0.313) or OS (p = 0.081); however, lines of salvage and response
prior to ASCT remain significantly prognostic for PFS (>1 line of
salvage: HR 2.14, 95% CI 1.592.87, p < 0.001; nonCR: HR 1.61, 95%
CI 1.262.05, p < 0.001) and OS (>1 line of salvage: HR 2.25, 95% CI
1.663.05, p < 0.001; nonCR: HR 1.63, 95% CI 1.262.12, p < 0.001).
Conclusions: In patients with RR DLBCL following frontline immu-
nochemotherapy, requiring more than 1 line of salvage therapy and
failure to achieve CR are strong independent risk factors for poor
PFS and OS after ASCT. Novel therapies such as CART cell therapy
should be studied in this population.
EA previously submitted to ASCO 2021.
Keywords: Aggressive Bcell nonHodgkin lymphoma, Combination
Therapies, Stem Cell Transplant
Conflicts of interests pertinent to the abstract
M. KharfanDabaja
Consultant or advisory role: Daiichi Sankyo
187 | AUTOLOGOUS TRANSPLANT IN ELDERLY PATIENTS
WITH R/R AGGRESSIVE LYMPHOMA SELECTED BY SIMPLIFIED
CGA: THE RECANZ PROSPECTIVE PHASE 2 STUDY BY THE
FONDAZIONE ITALIANA LINFOMI
A. Tucci
1
, G. Musuraca
2
, F. Cavallo
3
, V. R. Zilioli
4
, M. Zanni
5
,
S. Pelliccia
6
, D. Mannina
7
, M. Michieli
8
, D. Vallisa
9
, M. Tani
10
,
F. Merli
11
, F. Re
12
, L. Marcheselli
13
, G. Campostrini
1
, C. Pagani
1
,
D. Grimaldi
3
, E. V. Liardo
2
, A. Re
1
, M. C. Cox
14
, G. Rossi
1
1
ASST Spedali Civili Brescia, Hematology Division, Brescia, Italy,
2
IRCCS
Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”,
Hematology Unit, Meldola (FC), Italy,
3
University of Torino/AOU “Città
della Salute e della Scienza di Torino”, Division of Hematology,
Department of Molecular Biotechnologies and Health Sciences, Torino,
Italy,
4
ASST Grande Ospedale Metropolitano Niguarda, Division of
Hematology, Milano, Italy,
5
A.O. SS. Antonio e Biagio e Cesare Arrigo,
Division of Hematology, Alessandria, Italy,
6
Hospital Sant’Andrea
Sapienza, Rome, Hematology, University, Roma, Italy,
7
Azienda
Ospedaliera Papardo, Unit of Hematology, Messina, Italy,
8
Aviano (PN),
Haematology Transplant and Cell Therapy Unit, Aviano (PN), Italy,
9
Ospedale Guglielmo da Saliceto, Division of Hematology, Piacenza, Italy,
10
Ospedale delle Croci, Department of Hematology, Ravenna, Italy,
11
Azienda Unità Sanitaria Locale IRCCS, Hematology Unit, Reggio
Emilia, Italy,
12
AOU di Parma, Hematology Unit, Parma, Italy,
13
Fondazione Italiana Linfomi Onlus, Fondazione Italiana Linfomi Onlus,
Modena, Italy,
14
University Hospital Sant’Andrea Sapienza, Hematology,
Roma, Italy
Introduction: Relapsed/refractory (R/R) aggressive B cell lym-
phoma has a poor prognosis especially in the postRituximab era.
Platinumbased salvage treatment followed by autologous stem
cell transplantation (ASCT) is still standard treatment in young
patients (pts). However, more than 60% of pts are older than 65
and represent an unmet need. We have recently demonstrated
that a simplified comprehensive geriatric assessment (sCGA) can
identify elderly lymphoma pts fit for intensive firstline treatment.
We have conducted a multicentre study aiming at evaluating
the feasibility of an ASCT program in elderly R/R aggressive
lymphoma pts.
Methods: Patients with R/R aggressive lymphoma after one line of
treatment, age 6575, and FIT to sCGA were included. Recommended
treatments were RDHAP, RICE or gemcitabinecontaining
264
-
SUPPLEMENT ABSTRACTS
regimens, with PBSC mobilisation after 12 cycles. Patients FIT to a
second sCGA evaluation achieving at least partial response after 3
salvage courses were eligible for ASCT and were conditioned with
either BEAM or FEAM.
Results: Seventy pts were enrolled by 16 FIL centres from May
2014 to August 2019. Fortythree pts did not reach ASCT because
of progressive (32) or stable (4) disease, death (heart failure and
septic shock) (2), personal/physician decision (4/1). ASCT was
performed in 27 pts; a median of 5.6 x 106 CD34/Kg were
infused. Table 1a shows their demographic and clinical character-
istics. No differences emerged between pts reaching ASCT or not.
By intention to treat analysis 2y overall survival (OS) and PFS of
the 70 pts enrolled were 65% (95%CI: 5076%) and 34% (95%CI:
2246%) respectively, without differences according to age (table
1b). After a median of 27 months, OS after ASCT was 79% (95CI:
5186%) and EFS 56% (95CI: 3275%). Twentyfour pts obtained a
CR; three pts progressed 18 months after ASCT and died. Most
common nonhematologic grade 34 AE were gastrointestinal
(11%) and infectious (6.5%).
Conclusion: This study confirms the poor response to IIline
chemotherapy of elderly pts with R/R aggressive lymphoma
selected by sCGA. However, it highlights the feasibility and high
efficacy of ASCT in responding pts. These results represent a useful
comparator for the evaluation of feasibility and efficacy of innovative
approaches like CART cells or bispecific antibodies in the same age
groups.
Keywords: Aggressive Bcell nonHodgkin lymphoma Stem Cell
Transplant
No conflicts of interest pertinent to the abstract.
188 | ALLOGENEIC HEMATOPOIETIC STEM CELLS
TRANSPLANTATION FOR NONHODGKIN'S LYMPHOMA IN
SWITZERLAND. 35 YEARS OF EXPERIENCE 19852020. FOR SBST
WORKING GROUP
M. Nabergoj
1
, B. Grandjean
2
, P. Stakia
1
, A. Stern
3
, M. Medinger
4
,
H. Baldomero
4
, S. MasouridiLevrat
1
, C. Dantin
1
, A. Rovo
2
,
K. Ritter
5
, U. Schanz
5
, J. Passweg
4
, Y. Chalandon
1
, E. Rebmann
Chigrinova
2
1
University Hospital of Geneva, HUG, Hematology, Geneva, Switzerland,
2
University Hospital of Bern, Inselspital, Hematology and central
laboratory, Bern, Switzerland,
3
Réseau hospitalier neuchâtelois, Oncology
hematology department, Neuchâtel, Switzerland,
4
University Hospital of
Basel, Hematology, Basel, Switzerland,
5
University Hospital of Zurich,
Hematology, Zurich, Switzerland
Background: despite the development of new highly effective
treatments in the field of NonHodgkin's lymphoma (NHL), allo-
geneic hematopoietic stem cell transplantation (alloHSCT) still
remains a potentially curative option for virtually all type of NHL.
Due to concerns about its high toxicity, alloHSCT in NHL is
reserved as the ultimate line of treatment. Introduction of reduced
intensity conditioning regimens, usage of Tdepletion methods,
amelioration of supportive care and graftversus –host (GvHD)
disease treatment have globally decreased the NRM rates, making
the use of alloHSCT an attractive alternative in a setting of
relapse/refractory NHL. Here we report the 35 years of Swiss
experience in alloHSCT for NHL.
Materials and Methods: The study included 301 patients who
received alloHSCT for NHL in one of the three University Hospitals
of Switzerland (Zurich, Basel and Geneva) between September 1985
and May 2020. The primary endpoint was OS. Secondary endpoints
were relapse free survival (RFS), nonrelapse mortality (NRM),
relapse incidence (RI), acute (aGVHD) and chronic (cGVHD) rates,
that were assessed in univariate analysis.
Results: Median followup was 61 months (24112). The median
age of patients at the time of alloHSCT was 51 years (1772), with
male gender prevalence 206 (68%). Bcell NHL were diagnosed in
217 (72%) cases, with the most frequent being DLBCL and CLL
subtypes (76 and 53 cases respectively). Tcell NHL were indica-
tion for alloHSCT in 84 (28%) cases. Prior autologous HSCT was
performed in 130 (43%) of patients. A good performance sta-
tus, according to Karnofsky index (80) was reported in 259
(90%). Hundred fortyfour (48%) patients were in CR and 32
(22%) of those were in first CR. A reduced conditioning regimen
(RIC) was applied in 167 (56%) patients. TBI was part of condi-
tioning regimen in 132 (44%) patients. Stem cell source was pe-
ripheral blood in 261 (87%) transplants. Donor was an HLA
identical sibling or an HLAmatched unrelated donor for 159
(53%) and 74 (25%) transplants, respectively. Successful neutrophil
engraftment occurred in 273 (98%) patients in a median of 14
days (1218).
Survival analysis: 5 and 10years OS was 55% (SE ± 5.6) and 51%
(SE ± 6.7), respectively, and 5 and 10years RFS was 44% (±7.1) and
38% (SE±8.9). According to the univariate analysis, patients trans-
planted at younger age (<50 years) in a good performance status
(Karnofsky index 80), those in CR, especially in the first one (vs.
second or above) and those transplanted with a HLAmatched sibling
showed significantly better OS and RFS survivals (p < 0.05). 5 and
10years NRM was 24% (±2.7) and 28% (±3.0), respectively, and RI
31% (±2.9) and 35% (±3.2).
Conclusions: Our retrospective analysis of a large group of mixed
type NHL with an extended follow up (maximum of 25 years) con-
firms the efficacy of alloHSCT with promising longterm OS, RFS and
acceptable NRM rate.
Keywords: Aggressive Bcell nonHodgkin lymphoma, Aggressive T
cell nonHodgkin lymphoma, Stem Cell Transplant
No conflicts of interest pertinent to the abstract.
SUPPLEMENT ABSTRACTS
-
265
HODGKIN LYMPHOMA
189 | AMAHRELIS : ADCETRIS MAINTENANCE AFTER
AUTOLOGOUS STEM CELL TRANSPLANTATION IN HODGKIN
LYMPHOMA : A REAL LIFE STUDY FROM SFGMTC AND LYSA
GROUPS
A. Marouf
1
, A. S. Cottereau
2
, S. Kanoun
3
, P. Deschamps
1
, P. Franchi
1
,
M. Meignan
4
, D. Sibon
5
, T. Gastinne
6
, C. Borel
7
, M. Hammoud
8
,
G. Sicard
9
, R. Gille
10
, D. Cavalieri
11
, A. Stamatoullas
12
, L. Clement
13
,
J. Lazarovici
14
, A. Chauchet
15
, L. M. Fornecker
16
, S. Amorin
17
,
M. Rocquet
1
, N. Raus
18
, B. Burroni
19
, M. T. Rubio
20
, O. Casasnovas
21
,
G. Cartron
22
, D. Bouscary
1
, P. Brice
23
, H. Ghesquieres
18
,
J. Tamburini
24
, B. Deau
1
1
Cochin Hospital, Paris University, Hematology Unit, Paris, France,
2
Cochin Hospital, Assistance PubliqueHôpitaux de Paris (APHP), Paris
Descartes University, Department of Nuclear Medicine, Paris, France,
3
Institut universitaire du cancer ToulouseOncopole, Nuclear Medecine
Unit, Toulouse, France,
4
Hôpital Henri Mondor, Paris Est University,
Lymphoma Study Association Imaging, Créteil, France,
5
Necker Hospital,
Paris University, Department of Hematology, Paris, France,
6
Nantes Uni-
versity Hospital, Department of Hematology, Nantes, France,
7
Institut
universitaire du cancer Toulouse Oncopole, Hematology, Toulouse,
France,
8
Lymphoid Malignancies Unit, Hôpital Henri Mondor, Hematology,
Creteil, France,
9
AixMarseille University, Hematology, Marseille, France,
10
Centre Léon Berard, Hematology, Lyon, France,
11
Centre Hospitalier
Universitaire Estaing, Hematology, Clermont Ferrand, France,
12
Centre
Henri Becquerel, Hematology, Rouen, France,
13
CHRU Nancy Brabois,
Hematology, Vandoeuvre Les Nancy, France,
14
Institut Gustave Roussy,
Hematology, Villejuif, France,
15
CHU Besançon, Hematology, Besançon,
France,
16
Strasbourg University Hospital,INSERM S1113, Hematology,
Strasbourg, France,
17
Hopital Saint Vincent de Paul, Hematology, Lille,
France,
18
Hopital Lyon Sud, Hematology, Pierre Benite, France,
19
Cochin
Hospital, APHP, Centre de recherche des Cordeliers, Sorbonne University,
INSERM, Paris University, Pathology, Paris, France,
20
CHRU Nancy, CNRS
UMR 7365, Équipe 6, Biopôle de L'Université de Lorraine, Hematology,
Vandoeuvre Les Nancy, France,
21
Dijon University Hospital, INSERM UMR
1231, Hematology, Dijon, France,
22
University of Montpellier, Hematol-
ogy, Montpellier, France,
23
Saint Louis Hospital, Paris university, Hema-
tology, Paris, France,
24
Université de Paris, Institut Cochin, INSERM
FIGURE 1 10years overall survival and nonrelapse mortality
266
-
SUPPLEMENT ABSTRACTS
U1016, F75014 Paris, Translational Research Centre in Onco
hematology, Faculty of Medicine, University of Geneva, 1211, Hematol-
ogy, Geneva, Switzerland
Introduction: AETHERA study (Moskowitz, Lancet 2015) showed
that Brentuximab Vedotin (BV) maintenance after autologous stem
cell transplantation (ASCT) improved progression free survival (PFS)
in BVnaive refractory/relapsed (R/R) Hodgkin lymphoma (HL) pa-
tients. However, since BV approval for R/R HL, many patients are
receiving salvage BV before ASCT, alone or combined with chemo-
therapy. In AMAHRELIS study, we investigated the outcome of pa-
tients mostly treated with BV in salvage and maintenance post
ASCT.
Methods: We conducted this observational retrospective cohort
study in 25 centers. Inclusion criteria were R/R HL patients who
received at least two infusions of BV after ASCT, at the exclusion of
patients in progression after transplant. Among 1134 patients who
underwent ASCT for R/R HL between 2012 and 2017 based on the
French society of bone marrow transplantation database, data were
available for 794 (70%) patients. FDGPET scan at relapse and before
transplantation were centrally reviewed and metabolic complete
remission (mCR) was defined by a Deauville score <4. As primary
objective, the 2 yearsPFS was assessed.
Results: A total of 115 patients were enrolled. 95% met inclusion
criteria for BV maintenance according to the AETHERA study as
primary refractory disease (43%), early relapse (27%) or extranodal
disease (49%). The mean number of BV injections after ASCT was 11
(318). Patients characteristics were : median age of 34 y (1668y),
54% were male, 43% patients had PRD, 28% an ER and 29% a relapse
>12 months. Notably, 70% of patients received BV as salvage ther-
apy. Among 91 patients eligible for FDGPET centrally review, 89%
(81/91) achieved a mCR before ASCT. The median followup period
was 35 months. The 2years survival for the whole cohort was 75,3%
for PFS (95% CI : 68,484,3) and 96,4% for OS (95% CI : 94,2100)
SUPPLEMENT ABSTRACTS
-
267
(Figures AB). The use of BV as part of salvage therapy before
transplant had no impact on outcome.
High risk patients according to the Lysa prognosis score, as
either primary refractory disease or early relapse and disseminated
disease, correlated significantly with a lower PFS. A subgroup anal-
ysis was subsequently conducted from two real life studies Amah-
relis and HR2009 (Deau, BJH 2018) to compare two consolidation
strategies in high risk patients, either BV maintenance or a second
ASCT. This analysis was performed after onetoone propensity score
matching generated 24 pairs with wellbalanced baseline confound-
ing factors and with an adjustment on the propensity score on the
whole population, and showed a similar outcome on PFS, whereas BV
maintenance offers a better OS than a second ASCT (Figures CD).
Conclusion: From the reallife AMAHRELIS study, we confirmed the
favorable outcome of R/R HL patients in the era of BV maintenance.
Future studies incorporating BV strategies with immune checkpoint
inhibitors might improve outcome in high risk patients.
Keywords: Hodgkin lymphoma
Conflicts of interests pertinent to the abstract
B. Deau
Consultant or advisory role: Roche, Takeda
Research funding: Takeda
190 | LONGTERM FOLLOWUP AND BIOMARKER ANALYSES
OF BRENTUXIMAB VEDOTIN AND DHAP IN RELAPSED/
REFRACTORY HODGKIN LYMPHOMA PATIENTS: THE HOVON/
LLPC TRANSPLANT BRAVE STUDY
J. Driessen
1
, M. J. Kersten
1
, L. Visser
2
, A. van den Berg
2
,
J. M. Zijlstra
3
, S. H. Tonino
1
, G. J. Zwezerijnen
4
, R. Boellaard
4
,
P. J. Lugtenburg
5
, M. Hutchings
6
, M. Nijland
7
, R. D. Liu
1
,
F. Morschhauser
8
, P. Brice
9
, T. Gastinne
10
, D. de Jong
11
,
A. Hagenbeek
1
, W. J. Plattel
7
, A. Diepstra
2
1
Amsterdam UMC, University of Amsterdam, LYMMCARE, Cancer Center
Amsterdam, Department of Hematology, Amsterdam, Netherlands,
2
University of Groningen, University Medical Center Groningen,
Department of Pathology and Medical Biology, Groningen, Netherlands,
3
Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center
Amsterdam, Department of Hematology, Amsterdam, Netherlands,
4
Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center
Amsterdam, Department of Radiology and Nuclear Medicine, Amsterdam,
Netherlands,
5
Erasmus MC Cancer Institute, University Medical Center,
Department of Hematology, Rotterdam, Netherlands,
6
Rigshospitalet,
Department of Hematology, Copenhagen, Denmark,
7
University of
Groningen, University Medical Center Groningen, Department of
Hematology, Groningen, Netherlands,
8
Centre Hospitalier Universitaire,
Department of Hematology, Lille, France,
9
Hopital Saint Louis,
Department of Hematology, Paris, France,
10
Centre Hospitalier
Universitaire, Department of Hematology, Nantes, France,
11
Amsterdam
UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam,
Department of Pathology, Amsterdam, Netherlands
Background: Patients with relapsed/refractory classical Hodgkin
lymphoma (r/r cHL) generally have a poor prognosis. We have shown
that brentuximab vedotin (BV) in combination with DHAP (dexa-
methasone, cytarabine, cisplatin) is highly effective with manageable
toxicity. Here we present the longterm followup, and also thymus
and activation regulated chemokine (TARC) and metabolic tumor
volume (MTV) analyses.
Methods: Patients were treated with 3 cycles of BVDHAP followed by
autologous stemcell transplant (ASCT). Serum was collected at base-
line, after each cycle, after ASCT and during followup. Soluble (s)TARC
was measured byELISA. Immunohistochemical (IHC) staining was done
for TARC on the lymph node biopsy at baseline. Baseline
18
FFDG
PETCT scans were analyzed for MTV using a threshold of standard
uptake value (SUV) 4.0. Prognostic value of biomarkers for time to
progression (TTP) was assessed by logrank survival analysis.
Results: Sixtyfive patients, of whom 46% had primary refractory
disease, were included. Central pathology review confirmed cHL
diagnosis in 58/65 patients. Patients with other histologies were
excluded from biomarker analyses, but not from clinical evaluation
per intention to treat. After a median followup of 39 months, the 3
year progression free survival (PFS) was 77% (95%CI: 7088) and the
overall survival (OS) was 95% (95%CI: 90100).
Of confirmed cHL patients (n = 58), seven patients (12%) had
weak or no TARC IHC staining in the HodgkinReed Sternberg (HRS)
cells and showed lower serum sTARC levels compared to patients
with positive TARC staining (median 608 vs 3701 pg/mL; p = 0.04).
cHL patients with no/weak TARC staining had a lower 3year TTP
rate (57% vs 93%, respectively; p < 0.001).
Based on levels in healthy controls, cHL patients with a baseline sTARC
< 1000 pg/ml (n = 14) were excluded in the subsequent sTARC ana-
lyses. sTARC decreased significantly after 1 cycle of BVDHAP (p <
0.001; Figure 1A), and patients with sTARC < 1000 pg/mL after 1 cycle
of BVDHAP had a 3year TTP of 91% vs 55% for patients with sTARC
1000 pg/mL at that timepoint (p = 0.01; Figure 1B).
Baseline MTV correlated with baseline sTARC (r = 0.53; p < 0.001).
Interim PET evaluation after 3 cycles of BVDHAP showed a a
complete metabolic response (CMR) in 47 patients and a partial
response (PR) in 5 patients. Patients with a CMR had a 3year TTP of
93% vs 40% for patients with a PR (p < 0.001).
Conclusion: Longterm followup of r/r cHL patients treated with BV
DHAP shows a high 3year PFS and OS. Serum sTARC correlates with
baseline MTV and can be used as an early response marker already
after 1 cycle of BVDHAP. Interim PET status is a strong prognostic
factor for postASCT TTP. In addition, we have identified low TARC
expression in HRS cells as a possible poor prognostic factor. Risk
assessment using different biomarkers could help guide treatment
decisions in an era with new targeted treatment options for r/r cHL.
EA previously submitted to EHA 2021.
The research was funded by: The study drug (BV) was provided for
the study and the study was funded by Takeda. Takeda did not have
268
-
SUPPLEMENT ABSTRACTS
any influence on the analysis of the data or the interpretation of the
results.
Keywords: Diagnostic and Prognostic Biomarkers, PETCT, Hodgkin
lymphoma
Conflicts of interests pertinent to the abstract
J. Driessen
Educational grants: Takeda (ASH conference 2019)
M. J. Kersten
Honoraria: Millennium/Takeda
Research funding: Millennium/Takeda
J. M. Zijlstra
Consultant or advisory role: Millennium/Takeda
Educational grants: Takeda (ASH 2019)
P. J. Lugtenburg
Consultant or advisory role: Millennium/Takeda
Research funding: Millennium/Takeda
M. Hutchings
Consultant or advisory role: Millennium/Takeda
Research funding: Millennium/Takeda
P. Brice
Honoraria: Millennium/Takeda
Research funding: Millennium/Takeda
T. Gastinne
Honoraria: Millennium/Takeda
D. de Jong
Consultant or advisory role: Millennium/Takeda
SUPPLEMENT ABSTRACTS
-
269
A. Hagenbeek
Consultant or advisory role: Millennium/Takeda
Honoraria: Millennium/Takeda
Research funding: Millennium/Takeda
A. Diepstra
Consultant or advisory role: Millennium/Takeda
Research funding: Millennium/Takeda
191 | BEGEV SALVAGE REGIMEN IN RELAPSED/
REFRACTORY CLASSICAL HODGKIN LYMPHOMA: A REALLIFE
EXPERIENCE
A. Morigi
1
, V. Stefoni
1
, L. Argnani
1
, M. Carella
1
, B. Casadei
1
, G. Lolli
1
,
A. Broccoli
1
, C. Pellegrini
1
, L. Nanni
1
, P. E. Coppola
1
, M. Gentilini
1
,
G. Bagnato
1
, P. L. Zinzani
1
1
IRCCS Azienda OspedalieroUniversitaria di Bologna Istituto di
Ematologia “Seràgnoli”, and Dipartimento di Medicina Specialistica,
Diagnostica e Sperimentale Università di Bologna, n/a, Bologna, Italy
Introduction: Any strategy aimed at achieving a minimal disease
status, and at specifically obtaining a positron emission tomography
negative status before autologous stem cell transplantation (ASCT)
without severe toxicity in primary relapsed/refractory Hodgkin
lymphoma (HL) patients would represent a major advance in the
overall management in this setting.
Methods: A singlecenter observational retrospective study was
conducted to assess effectiveness and safety of BEGEV (bendamus-
tine, gemcitabine and vinorelbine) regimen as first salvage setting
prior to ASCT in HL patients.
Results: In total, 23 patients (14 men and 9 women) were treated in
our institution between October 2017 and September 2019. Me-
dian age at BEGEV time was 39.6 years (range 17.2– 70.0), and the
median time from frontline therapy to first cycle of BEGEV was 1.3
months (range 1–8). At the end of BEGEV treatment, 21 out of the
23 patients, achieved a complete response (CR), with an ORR of
91.3%. All the patients underwent ASCT. With a median followup
time of 15 months, 2 CR patients had disease relapse, yielding an
estimated DFS of 86.7% at 26.6 months. The estimated OS was
95.5% at 27 months and the 2year PFS was 81.4%, respectively.
Response to firstline chemotherapy did not significantly influence
prognosis. BEGEV regimen was well tolerated by most patients, and
reversible hematological toxic effects were the most common
adverse events.
Conclusions: These first reallife data on BEGEV regimen as first
salvage setting in HL showed a relevant rate of objective responses
and a limited myelotoxicity with no impairment of a subsequent
mobilization of peripheral blood stem cells.
Keywords: Hodgkin lymphoma, Therapeutics and Clinical Trials in
Lymphoma Other
No conflicts of interest pertinent to the abstract.
192 | CAMRELIZUMAB COMBINED WITH GEMOX IN
PATIENTS WITH RELAPSED OR REFRACTORY HODGKIN
LYMPHOMA
Y. Xie
1
, L. Mi
1
, W. Zheng
1
, L. Ping
1
, N. Lin
1
, M. Tu
1
, C. Zhang
1
, Z. Ying
1
,
W. Liu
1
, L. Deng
1
, M. Wu
1
, T. Du
1
, Y. Tang
1
, X. Wang
1
, J. Zhu
1
, Y. Song
1
1
Key laboratory of Carcinogenesis and Translational Research (Ministry of
Education), Peking University Cancer Hospital & Institute, Department of
lymphoma, beijing, China
Objective: PD1antibody has shown remarkable efficacy in relapsed
or refractory Hodgkin lymphoma (R/R HL). Here we designed a
clinical trial to evaluate the efficacy and safety of PD1 antibody
camrelizumab combined with GEMOX chemotherapy in R/R HL pa-
tients. The preliminary results had been obtained.
Method: This is an openlabel, singlecenter, nonrandomized, phase
2 study (NCT04239170). The main inclusion criteria include age18,
ECOG < 2, histopathology confirmed classical HL, number of previ-
ous chemotherapy regimen 1 but <3, having measurable lesion(s)
assessed by Lugano 2014 criteria and preparing to receive autolo-
gous stem cell transplantation (ASCT). The treatment schedule is
shown in Figure 1. The primary endpoint is the proportion of patients
who achieved PETCTconfirmed complete response (CR) according
to Lugano 2014 criteria.
Results: From March 2020 to February 2021, 14 patients were
enrolled. One patient was excluded because of the diagnosis of
diffused large Bcell lymphoma in the second biopsy. The remaining
13 patients ranged in age from 22 to 48, with a maletofemale ratio
of 8:5. Among the 13 patients, nine patients failed to response in the
last treatment. Among the 4 relapsed cases, 2 of them recurred
within one year and 3 of them had extranodal invasion. At the first
tumor response evaluation, 61.5% (8/13) patients achieved CR and
30.8% (4/13) patients achieved PR, resulting an ORR of 92.3%. Only
one patient had stable disease (SD). The 5 patients who had PR or SD
received an additional cycle of camrelizumab plus GEMOX treatment,
and 3 of them had a second tumor response results, in which one
patient who had PR in the first evaluation was found to achieve CR.
The remaining 2 patients were still waiting for evaluation. Up to now,
collection of the autologous hematopoietic stem cells was completed
in seven patients and the average number of CD34+ cells was 2.24
10
6
/kg. Most adverse events (AEs) were of grade 1 to 2. No grade 4
or above AEs occurred. AEs of grade 3 included neutropenia (2.3%)
and transfusion reaction (2.3%).
Conclusion: The preliminary data obtained so far suggests that
camrelizumab combined with GEMOX chemotherapy has encour-
aging clinical efficacy and tolerable toxicity in R/R HL patients and
merits continuous study.
Abbreviations: ASCT, autologous stemcell transplantation
*Patients who wait longer than 4 weeks to receive ASCT may be
considered to receive 1 or 2 camrelizumab monotherapy.
Keywords: Combination Therapies
No conflicts of interest pertinent to the abstract.
270
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SUPPLEMENT ABSTRACTS
193 | HEALTHRELATED QUALITY OF LIFE AMONG PATIENTS
WITH RELAPSED/REFRACTORY CLASSICAL HODGKIN
LYMPHOMA (R/R CHL) IN A PHASE 3 STUDY OF
PEMBROLIZUMAB VERSUS BRENTUXIMAB VEDOTIN
P. L. Zinzani
1
, M. Raut
2
, T. Saretsky
3
, R. Ramchandren
4
, A.
Santoro
5
, E. PaszkiewiczKozik
6
, R. Gasiorowski
7
, N. A. Johnson
8
, J.
S. R. de Oliveira
9
, V. Buccheri
10
, G. F. Perini
11
, M. Dickinson
12
,
A. McDonald
13
, M. Ozcan
14
, N. Sekiguchi
15
, H. Giezek
16
, A.
Nahar
17
, J. Kuruvilla
18
1
IRCCS Azienda Ospedaliero–Universitaria di Bologna Istituto di Ema-
tologia “Seràgnoli”, and Dipartimento di Medicina Specialistica, Diag-
nostica e Sperimentale Università di Bologna, Specialized, Diagnostic and
Experimental Medicine, Bologna, Italy,
2
Merck & Co., Inc., Department of
Medical Oncology, Kenilworth, New Jersey, USA,
3
Merck & Co., Inc.,
Department of Medical Oncology, Kenilworth, New Jersey, USA,
4
University of Tennessee, Department of Mediciine, Knoxville, Tennessee,
USA,
5
Humanitas University and IRCCS Humanitas Research Center,
Department of Oncology, Milan, Italy,
6
Maria Sklodowska–Curie Na-
tional Institute of Oncology, Department of Medical Oncology, Warsaw,
Poland,
7
Concord Hospital, University of Sydney, Department of He-
matology, Sydney, Australia,
8
Jewish General Hospital, Department of
Hematology, Montreal, Canada,
9
Casa de Saúde Santa Marcelina,
Department of Medical Oncology, São Paulo, Brazil,
10
Hospital das
Clinicas da Faculdade de Medicina da Universidade de São Paulo,
Department of Clinical Medicine, São Paulo, Brazil,
11
Hospital Israelita
Albert Einstein, Department of Hematology, São Paulo, Brazil,
12
Peter
MacCallum Cancer Centre and Royal Melbourne Hospital, Department
of Lymphoma Disease, Melbourne, Australia,
13
Pretoria East Hospital,
Department of Hematology, Pretoria, South Africa,
14
Ankara University
School of Medicine, Department of Internal Medicine, Ankara, Turkey,
15
National Hospital Organization Disaster Medical Center, Department
of Medical Oncology, Tokyo, Japan,
16
Merck & Co., Inc., Department of
Medical Oncology, Kenilworth, New Jersey, USA,
17
Merck & Co., Inc.,
Department of Medical Oncology, Kenilworth, New Jersey, USA,
18
Princess Margaret Cancer Centre, Department of Medical Oncology
and Hematology, Toronto, Canada
Introduction: In the openlabel, international, randomized, phase 3
KEYNOTE204 study (NCT02684292), the PD1 inhibitor pem-
brolizumab (pembro) improved progressionfree survival vs bren-
tuximab vedotin (BV) in patients (pts) with R/R cHL who were
ineligible for or failed autologous stem cell transplant (ASCT). Here
we report analyses of exploratory end points of pembro vs BV on
healthrelated quality of life (HRQoL) among R/R cHL pts from
KEYNOTE204.
Methods: Pts were randomized (1:1) to pembro 200 mg IV or BV
1.8 mg/kg IV Q3W. PRO analysis population included pts who
received 1 dose of study treatment and completed 1 PRO
assessment. European Organization for Research and Treatment of
Cancer (EORTC) QoL Questionnaire Core 30 (QLQC30) was
administered at baseline, Q6W until wk 24, and Q12W thereafter.
Prespecified exploratory end points included least square mean
(LSM) change from baseline to wk 24 and time to deterioration
(TTD; 10point decline from baseline) for global health status/
QoL (GHS/QoL), functioning scales (physical, role, emotional,
cognitive, and social), symptom scales (fatigue, nausea/vomiting,
pain), and symptom single items (dyspnea, insomnia, appetite loss,
constipation, diarrhea, financial difficulties). Differences between
groups were evaluated using twosided nominal P values not
controlled for multiplicity.
Results: Of 304 randomized pts, 296 (pembro, 146; BV, 150) were
in the PRO analysis. Compliance rates were >90% at baseline and
>80% at wk 24 in both groups. Higher scores on GHS/QoL and
functioning scales and lower scores on symptom scales indicate
better HRQoL. LSM change from baseline to wk 24 was higher
with pembro vs BV for the EORTC QLQC30 GHS/QoL (7.29 vs
1.31; LSM difference, 8.60; 95% CI, 3.89, 13.31; P = 0.0004)
physical (4.31 vs –1.93; LSM difference, 6.24; 95% CI, 1.87, 10.62;
P = 0.0054), role (6.86 vs –1.19; LSM difference, 8.04; 95% CI,
1.90, 14.19; P = 0.0105), and social (5.96 vs 0.54; LSM difference,
5.42; 95% CI, 95% CI, 0.18, 10.67; P = 0.0429) functioning scores.
No treatment differences in emotional and cognitive functioning
scores were observed. For symptom scales, LSM changes from
baseline to wk 24 were lower with pembro vs BV for the fatigue
(LSM difference, –11.88; 95% CI, –17.26, –6.50; P < 0.0001) and
FIGURE 1 Experiment design
SUPPLEMENT ABSTRACTS
-
271
pain (–6.03; –11.70, –0.36; P = 0.0371) scores; no treatment dif-
ferences for nausea/vomiting symptom scores were observed. LSM
change from baseline to wk 24 was lower with pembro vs BV in
all symptom singleitem scores except constipation and diarrhea
(Figure). Compared with BV, pembro prolonged TTD for EORTC
QLQC30 GHS/QoL, physical, role, emotional, and social func-
tioning scales and for EORTC QLQC30 fatigue and pain symptom
scales.
Conclusions: Pembro improved pt HRQoL compared with BV and
prolonged TTD. Findings further support pembro as the preferred
treatment option for pts with R/R cHL who are ineligible for or fail
ASCT.
The research was funded by: Merck Sharp & Dohme Corp., a sub-
sidiary of Merck & Co., Inc., Kenilworth, NJ, USA
Keywords: Hodgkin lymphoma, Immunotherapy
Conflicts of interests pertinent to the abstract
P. L. Zinzani
Consultant or advisory role: Roche, Janssen, Takeda, Eusapharma,
Incyte, Beigene, Kirin Kyowa, Takeda, Merck, Bayer, Novartis
Honoraria: Servier, AbbVie, Merck, Eusapharma, Novartis, Incyte;
Takeda Beigene, Janssen, Roche, Bayer, Sanofi, Kirin Kiowa
Other remuneration: Speaker bureau: Merck, Eusapharma, Takeda,
Novartis, Kirin Kiowa, Janssen, Roche, Incyte
M. Raut
Employment or leadership position: Merck & Co., Inc.
T. Saretsky
Employment or leadership position: Merck & Co., Inc.
Stock ownership: Merck & Co., Inc.
R. Ramchandren
Consultant or advisory role: Seattle Genetics
Research funding: Merck, Pharmacyclics, Beigene, BMS
A. Santoro
Consultant or advisory role: Bristol Myers Squibb, Servier, Gilead,
Pfizer, Eisai, Bayer, Merck Sharp & Dohme, Arqule, Sanofi
Other remuneration: Speaker bureau: Takeda, Bristol Myers Squibb,
Roche, AbbVie, Amgen, Celgene, Servier, Gilead, AstraZeneca, Pfizer,
Arqule, Lilly, Sandoz, Eisai, Novartis, Bayer, Merck Sharp & Dohme
E. PaszkiewiczKozik
Educational grants: Roche, Celgene, Takeda, AbbVie
R. Gasiorowski
Honoraria: MSD, AbbVie, Novartis, Astellas, Takeda
N. A. Johnson
Consultant or advisory role: Merck, BMS, Roche, Lundbeck, AbbVie,
Johnson and Johnson, Seattle Genetics
Honoraria: Merck, BMS, Roche, Lundbeck
V. Buccheri
Consultant or advisory role: AstraZeneca
Research funding: AstraZeneca, MSD, Takeda
Other remuneration: Speaker bureau: AstraZeneca
G. F. Perini
Consultant or advisory role: Janssen, AbbVie, Takeda, MSD,
AstraZeneca
Other remuneration: Speaker bureau: Janssen, AbbVie, Takeda, MSD,
AstraZeneca
M. Dickinson
Consultant or advisory role: Roche, MSD, Novartis, Gilead, Janssen
Honoraria: MSD, Roche, Amgen, Janssen, BMS, Novartis, Gilead
Research funding: MSD, Novartis, Roche, Takeda, Celgene
Other remuneration: Speaker bureau: Novartis
A. McDonald
Educational grants: Roche, Celgene, Takeda, AbbVie
LSM Changes From Baseline in EORTC QLQC30 Symptom Single Item Scale at Week 24
272
-
SUPPLEMENT ABSTRACTS
M. Ozcan
Honoraria: Takeda, Amgen
Research funding: Janssen, Celgene, Takeda, Archigen, Roche, Bayer,
MSD, AbbVie, Novartis
Educational grants: BMS, Jazz, Roche, Sanofi, Abdi İbrahim, Janssen,
Takeda, AbbVie, Amgen
N. Sekiguchi
Research funding: Ono, A2 Healthcare, Astellas, Janssen, Merck
Sharp & Dohme, Otsuka, Pfizer, PPDSNBL, Sumitomo Dainippon
Pharma, Daiichi Sankyo Company, Bristol Myers Squibb
H. Giezek
Employment or leadership position: Merck & Co., Inc.
A. Nahar
Employment or leadership position: Merck & Co., Inc.
J. Kuruvilla
Consultant or advisory role: AbbVie, BMS, Gilead, Karyopharm,
Merck, Roche, Seattle Genetics
Honoraria: Amgen, Antengene, Astra Zeneca, BMS, Gilead, Incyte,
Janssen, Karyopharm, Merck, Novartis, Pfizer, Roche, Seattle Ge-
netics, TG Therapeutics
Research funding: Canadian Cancer Society, Leukemia and Lym-
phoma Society Canada, Princess Margaret Cancer Foundation,
Janssen, Roche, AstraZeneca
Other remuneration: Data Safety Monitoring Board: Karyopharm
194 | REAL WORLD OUTCOMES AND RESPONSES TO
SECONDLINE THERAPY IN RELAPSED/REFRACTORY HODGKIN
LYMPHOMA: A MULTICENTRE UK STUDY
R. Shotton
1
, A. A. Kirkwood
2
, M. Northend
3
, D. Fathoala
3
, K. Burton
4
,
G. Ferguson
5
, L. Aiken
6
, C. Shrubsole
7
, L. Henry
8
, M. Owen
9
,
R. Oliver
10
, N. MartinezCalle
11
, A. Etherington
12
, E. GallopEvans
13
,
C. Burton
9
, F. Miall
8
, W. Osborne
7
, R. Le Dieu
6
, P. McKay
5
,
K. Ardeshna
3
, G. P. Collins
4
, E. Phillips
14
1
The Christie NHS Foundation Trust, Medical oncology, Manchester, UK,
2
UCL Cancer institute, University College London, Cancer Research UK and
UCL Cancer Trials Centre, London, UK,
3
University College Hospital,
University College London, Haematology Dept, London, UK,
4
Oxford
University Hospitals NHS Foundation Trust, Haematology Dept, Oxford,
UK,
5
Beatson West of Scotland Cancer Centre, Haematology Dept,
Glasgow, UK,
6
Bart's Health NHS Trust, HaematoOncology Dept, London,
UK,
7
Newcastle upon Tyne Hospitals NHS Foundation Trust, Haematology
Dept, Newcastle, UK,
8
University Hospitals of Leicester, Haematology Dept,
Leicester, UK,
9
Leeds Cancer Centre, , Leeds, UK,
10
University Hospitals
Bristol, Haematology Dept, Bristol, UK,
11
Nottingham University Hospitals,
Haematology Dept, Nottingham, UK,
12
Velindre Cancer Centre, Haema-
tology, Cardiff, UK,
13
Velindre Cancer Centre, Clinical Oncology, Cardiff,
UK,
14
The Christie NHS Foundation Trust, NIHR Manchester Biomedical
Research Centre and University of Manchester, Manchester, UK
Introduction: For patients (pts) with relapsed or refractory (R/R)
Hodgkin lymphoma (HL), the aim of secondline (2L) treatment is to
achieve complete metabolic response (CMR) prior to highdose
chemotherapy and autologous stem cell transplant (ASCT). Inten-
sive chemotherapy is commonly used, but there is no standard of
care and CMR rates using contemporary fluorodeoxyglucose
positron emission tomography (PET) assessment are unknown.
Novel agents have shown promise, but comparative data with con-
ventional 2L chemotherapy are lacking. We aimed to assess response
to 2L chemotherapy according to the Lugano classification.
Methods: This retrospective study includes all pts with R/R HL who
received intensive 2L chemotherapy with intent to consolidate with
ASCT at 11 UK centres between 01/01/2015 and 31/12/2019. PET
response was locally assessed using Deauville criteria (DS). CMR was
defined as a DS of 13. Survival was measured from start of 2L
treatment.
Results: 252 pts were included: 58% were male and median age at 2L
treatment was 32y (range 1670). 87% had received ABVD as initial
frontline (1L) treatment. 44% had refractory disease, 20% had early
relapse (312m from end of 1L) and 36% late relapse. Extranodal
disease was present in 46%, B symptoms in 30% and anaemia in 15%
(haemoglobin (Hb) < 120/< 105 g/L for men/women).
The most common 2L regimens were ESHAP (N = 95, 38%), GDP/
GEMP (N = 61, 24%), IGEV (N = 50, 20%) and IVE (N = 29, 12%),
primarily determined by centre preference. Treatment was changed
due to toxicity in 9 pts (4%). There were no treatmentrelated deaths.
In total, 49% achieved CMR, 27% partial response, 7% stable disease
and 18% progressive disease. CMR rates were 40% with ESHAP, 54%
with GDP/GEMP, 54% with IGEV, 55% with IVE and 30% with other
intensive regimens (N = 17). In pts with refractory disease, 36% had
CMR, vs 47% for early relapse and 60% for late relapse. In multi-
variable analysis, CMR was significantly associated with late vs early
relapse or refractory disease (odds ratio (OR) 2.32 (1.30 4.13), p =
0.004). There was a trend towards lower CMR rates for pts with
anaemia (OR 0.49 (0.22 1.09), p = 0.08). There was no association
with choice of 2L regimen.
Median followup was 28 months. In total, 121 pts (48%) received
SCT after 2L treatment (120 ASCT; 1 allogeneic), of which 104
(86%) had CMR preASCT. 2 pts with CMR failed stem cell harvest.
Median progressionfree survival (PFS) for all pts was 35 months
(Figure). 2year PFS and overall survival rates were 54% and 87%,
respectively. For pts with CMR after 2L who received ASCT, 2year
PFS was 79%.
Conclusions: In this large cohort of pts with R/R HL, CMR rates after
2L treatment were strongly associated with duration of response to
1L treatment, but not choice of 2L chemotherapy. Outpatient regi-
mens such as GDP had similar efficacy to inpatient regimens. CMR
and ASCT rates were suboptimal, highlighting a need to evaluate
novel regimens in this setting.
Keywords: Hodgkin lymphoma, Chemotherapy, Stem Cell
Transplant
No conflicts of interest pertinent to the abstract.
SUPPLEMENT ABSTRACTS
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273
195 | CLINICAL OUTCOMES OF RELAPSED HODGKIN
LYMPHOMA PATIENTS AFTER CONTEMPORARY FIRSTLINE
TREATMENT: RESULTS FROM THE GERMAN HODGKIN STUDY
GROUP
P. J. Bröckelmann
1
, H. Müller
1
, S. Gillessen
1
, X. Yang
2
, L. Koeppel
3
,
V. Pilz
3
, P. Marinello
2
, P. Kaskel
3
, M. Raut
2
, M. Fuchs
1
,
P. Borchmann
1
, A. Engert
1
, B. von Tresckow
4
1
Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO
ABCD), University of Cologne, Department I of Internal Medicine and
German Hodgkin Study Group (GHSG), Cologne, Germany,
2
Merck & Co.,
Inc., Kenilworth, USA,
3
MSD Sharp & Dohme, GmbH, Haar, Germany,
4
University Hospital Essen, University of DuisburgEssen, Department of
Hematology and Stem Cell Transplantation, West German Cancer Center,
Essen, Germany
Introduction: The relative benefit of targeted agents increasingly
investigated and applied in relapsed or refractory Hodgkin
lymphoma (rrHL) is difficult to estimate due to a lack of ran-
domized trials. This retrospective study hence aimed to evaluate
disease characteristics, treatment patterns and associated out-
comes at first occurrence of rrHL after contemporary firstline
treatment.
Methods: We retrospectively identified patients with sufficiently
documented first rrHL initially receiving standard of care 1
st
line treatment in the GHSG HD13 (earlystage favorable), HD14
(earlystage unfavorable) and HD15 (advancedstage) trials. We
additionally evaluated rrHL patients enrolled in the placebo
controlled randomized GHSG HDR3i trial comparing conventional
DHAP vs. everolimus + DHAP salvage therapy prior planned
autologous stemcell transplantation (ASCT). We assessed overall
survival (OS) starting with date of 1
st
rrHL and ending with date of
death for any reason and progression free survival (PFS) measured
from date of rrHL to second rrHL or death from any reason. Pa-
tient, disease and treatment characteristics were analyzed with
descriptive statistics and survival endpoints with KaplanMeier
estimates.
Results: A total of 437 patients with first rrHL (HD13: n = 87, HD14:
n = 118, HD15: n = 188, HDR3i: n = 44) were identified. Of these
402 with sufficient documentation and followup were assessed with
a median age of 37.5 years (18.476.8). Time to relapse was 12
months in 49% and stage III/IV rrHL present in 52% of patients. High
dose chemotherapy and autologous stemcell transplantation (ASCT)
with and without consolidation was administered in 20% and 52% of
patients, respectively. The remaining 111 patients (27%) did not
receive ASCT mostly due to insufficient response to salvage
chemotherapy, advanced age, localized disease or patients’ prefer-
ence. Overall, 10year PFS and OS after first relapse were 48.2%
(95% confidence interval CI: 42.0%54.4%) and 59.3% (95%CI:
53.2%65.4%), respectively (Figure 1). Patients unsuitable for ASCT
had less favorable 10year PFS (32.5%, 95%CI: 19.1%45.9%) and OS
(41.9%, 95%CI: 28.1%55.6%). Significantly inferior PFS and OS was
also observed in primary refractory patients (10year PFS 36.0%,
95%CI: 24.2%47.9%; 10year OS 44.5%, 95%CI: 31.6%56.6%) and
those with stage IV disease at rrHL (10year PFS 29.3%, 95%CI:
18.5%40.9%; 10year OS 39.6%, 95%CI: 27.9%51.1%). Outcomes in
these higher risk patients appeared more favorable with ASCT than
without ASCT.
Conclusions: Our analysis of relapse and treatment patterns after
contemporary HL therapy provides a robust benchmark to evaluate
novel therapeutic strategies in rrHL. We confirm the curative po-
tential of current rrHL treatments including nonASCT approaches
and roughly 50% of rrHL patients do not experience a consecutive
relapse after 2
nd
line treatment.
EA previously submitted to EHA 2021.
The research was funded by: Merck Sharp & Dohme Corp., Kenil-
worth, NJ, USA
Keywords: Hodgkinlymphoma, Chemotherapy, StemCellTransplant
Conflicts of interests pertinent to the abstract
X. Yang
Employment or leadership position: Merck Sharp & Dohme Corp., USA
Stock ownership: MERCK & CO., INC.
PFS all patients (A), PFS all patients receiving an SCT after 2L theraphy (B)
274
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SUPPLEMENT ABSTRACTS
L. Koeppel
Employment or leadership position: MSD Sharp & Dohme GmbH,
Germany
V. Pilz
Employment or leadership position: MSD Sharp & Dohme GmbH,
Germany
P. Marinello
Employment or leadership position: MSD Sharp & Dohme Corp., USA
Stock ownership: MERCK & CO., INC.
P. Kaskel
Employment or leadership position: MSD Sharp & Dohme GmbH,
Germany
Stock ownership: MERCK & CO., INC.
M. Raut
Employment or leadership position: MSD Sharp & Dohme Corp., USA
Stock ownership: MERCK & CO., INC.
B. von Tresckow
Research funding: Merck Sharp & Dohme
FIGURE 1 PFS (panel A) and OS (B) after rrHL in patients treated in HD13, HD14, HD15, HDR3i
SUPPLEMENT ABSTRACTS
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275
196 | PETADAPTED THERAPY AFTER THREE CYCLES OF
ABVD FOR ALL STAGES OF HODGKIN LYMPHOMA: LONG TERM
FOLLOW UP OF THE GATLA LH05 TRIAL
A. Pavlovsky
1
, L. Fiad
2
, I. Fernandez
1
, V. Prates
2
, N. Kurgansky
3
,
A. Cerutti
4
, F. Sackman
1
, F. Negri
5
, L. Zoppegno
6
, P. Negri
5
,
G. Remaggi
1
, L. Ferrari
1
, R. Mariano
7
, L. Guanchiale
8
, J. Maradei
9
,
S. Rudoy
10
, F. Giuliani
1
, E. Roveri
11
, A. Enrico
12
, S. Zabaljauregui
13
,
M. Cabrejo
14
, C. Gumpel
15
, A. Quartara
16
, C. M. Gonzalez
13
,
A. Varela
17
, M. Riddick
18
, S. Pavlovsky
19
1
Fundaleu, Hematology, Buenos Aires, Argentina,
2
Hospital Italiano La
Plata, Hematology, Buenos Aires, Argentina,
3
Clínica Doctus, Hematology,
Santa Fe, Argentina,
4
IDHEA Clínica Hematológica, Hematology, Rosario,
Santa Fe, Argentina,
5
Instituto Privado de Hematología y Hemoterapia,
Hematology, Paraná, Entre Ríos, Argentina,
6
HIGA General José de San
Martín La Plata, Hematology, Buenos Aires, Argentina,
7
Hospital San
Martín, Hematology, Paraná, Entre Ríos, California, Argentina,
8
Hospital
Universitario Privado de Córdoba, Hematology, Córdoba, Argentina,
9
Hospital Municipal Dr. E. Ferreyra, Hematology, Necochea, Buenos Aires,
Argentina,
10
Clínica Modelo de Morón, Hematology, Buenos Aires,
Argentina,
11
Hospital Provincial del Centenario, Hematology, Rosario,
Santa Fe, Argentina,
12
Hospital Italiano La PLata, Hematology, Buenos
Aires, Argentina,
13
Instituto de Investigaciones Hematológicas Mariano R.
Castex, Hematology, Buenos Aires, Argentina,
14
Sanatorio Municipal Julio
Méndez, Hematology, Buenos Aires, Argentina,
15
Sanatorio Plaza,
Hematology, Rosario, Santa Fe, Argentina,
16
Hospital Provincial del
Centenario, Hematology, Rosario, Santa Fe, Argentina,
17
Sanatorio Las
Lomas, Hematology, Buenos Aires, Argentina,
18
Departamento de
MatematicasFacultad de Ciencias Exactas UNLPCONICET, Mathe-
matics, Buenos Aires, Argentina,
19
Fundaleu, Hematology, Buenos Aires,
Argentina
PET CT adapted treatment for first line Hodgkin Lymphoma has been
widely studied in the last decades. Longterm followup is important
to judge both efficacy and safety of this approach.
Patients and Methods: We analyzed updated followup data on all
patients (pts.) treated within the LH05 GATLA trial. Newly diag-
nosed pts. with HL Stages IIV were included. All patients received 3
ABVD and were evaluated with a PETCT (PETCT+3). Pts. with a
negative PETCT+3 (DS 1 and 2) were considered in metabolic CR
and received no further therapy. Pts with DS 3 and 4 completed 6
ABVD and IFRT on PETCT positive areas. Pts with progressive dis-
ease (DS 5) after 3 ABVD received salvage chemotherapy. With a
median age of 35 yrs., 300 presented with localized stage and 190
with advanced stage.
Results: In LH05 of all pts. 338 (69%) achieved CR with negative
PETCT+3, 152 (31 %) were PETCT+3 positive. With a median
follow up of 120 months the EFS and OS for all pts. at 5 years is 79.2%
and 94.3% respectively. Pts with negative PETCT+3 had an EFS of
89% and 80% for localized and advanced stage, compared to 63% for
276
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SUPPLEMENT ABSTRACTS
all pts. with positive PETCT+3 (p < 0.0001). We perform a multi-
variate analysis for EFS which included age, stage, IPS, bulky disease,
extranodal areas and the result of the PET+3. This last parameter
together with age were the only ones with statistical significance (p =
0.001 and 0.046 respectively). Stage at diagnosis was not significant.
With long term follow up the OS at 5 years is 97.3% and 87.3% for all
PET+3 negative vs PET+3 positive pts.
When comparing the results LH05 with our previous clinical trial
(LH96) there is no difference in EFS and OS at 5 years but in LH05
only 31% received more than 3 cycles of ABVD and IFRT compared
to 61% and 100% in LH96. This PET adapted approach reduces
exposure to chemo and radiotherapy with no negative effect on long
term outcome.
Conclusion: This long term follow up data support the PETCT
adapted approach for all stages of HL after a short course of
ABVD. In the Cox regression model, PETCT at completion of
treatment was the most significant factor associated to EFS.
Treatment with 3 cycles of ABVD can be adequate for pts. with
negative PETCT+3 regardless their stage at diagnosis. Nevertheless,
this long term follow up demonstrated that there is still room for
improvement trying to identify PETCT+3 negative patients that will
relapse and escalating treatment in PETCT+3 positive patients to
improve outcome. GATLA is designing a trial with the aim to improve
these two different risk groups.
Keywords: Hodgkin lymphoma
No conflicts of interest pertinent to the abstract.
197 | MODIFICATION OF ESCALATED BEACOPP WITH
DACARBAZINE SUBSTITUTION REDUCES TOXICITY WHILE
MAINTAINING EFFICACY FOR THE TREATMENT OF ADVANCED
STAGE HODGKIN LYMPHOMA
A. Santarsieri
1
, K. Sturgess
1
, P. Brice
2
, T. F. Menne
3
, W. Osborne
3
, T.
Creasey
4
, K. M. Ardeshna
5
, S. Behan
1
, K. Bhuller
6
, S. Booth
7
, G. P.
Collins
7
, K. Cwynarski
5
, M. Furtado
8
, S. Iyengar
9
, S. G. Jones
10
, D.
O'Mahony
11
, N. MartinezCalle
12
, P. McKay
13
, S. K. Nagumantry
14
, J.
F. Rudge
15
, N. Shah
16
, G. Stafford
1
, A. Sternberg
17
, B. J. Uttenthal
1
, A.
K. McMillan
12
, G. A. Follows
1
1
Cambridge University Hospitals NHS Foundation Trust, Haematology,
Cambridge, UK,
2
Hôpital SaintLouis, HématologieOncologie, Paris,
France,
3
Freeman Hospital, Newcastle Upon Tyne Hospitals NHS Foun-
dation Trust, Haematology, Newcastle, UK,
4
Newcastle University Hos-
pitals NHSFT, Haematology, Newcastle, UK,
5
University College London
Hospitals NHS Foundation Trust, Haematology, London, UK,
6
University
Hospitals of Leicester NHS Trust, Haematology, Leicester, UK,
7
Oxford
University Hospitals NHS Foundation Trust, Haematology, Oxford, UK,
8
Royal Cornwall Hospitals NHS Trust, Haematology, Cornwall, UK,
9
The
Royal Marsden NHS Foundation Trust, Haematology, London, UK,
10
Sherwood Forest Hospitals NHS Foundation Trust, Haematology, Not-
tinghamshire, UK,
11
Cork University Hospital, Oncology, Cork, Ireland,
12
Nottingham University Hospitals NHS Trust, Haematology, Nottingham,
UK,
13
Beatson West of Scotland Cancer Centre, Haematology, Glasgow,
UK,
14
Peterborough City Hospital, North West Anglia NHS Foundation
Trust, Haematology, Peterborough, UK,
15
Bullard Laboratories, University
of Cambridge, Cambridge, UK,
16
Norfolk and Norwich University Hospi-
tals NHS Foundation Trust, Haematology, Cambridge, UK,
17
Great
Western Hospitals NHS Foundation Trust, Haematology, Swindon, UK
In the treatment of advanced Hodgkin lymphoma, it is increasingly
common practice to modify escalated BEACOPP (eBPP) by removing
oral procarbazine and replacing it with IV dacarbazine (250mg/m2
D23) to reduce haematopoietic stem cell and gonadal toxicity.
However, published data of the “escalated BEACOPDac (eBPDac)”
regimen are limited.
From 2009, 205 patients were treated first line with either eBPP (n
= 58) at 4 UK centres, or eBPDac (n = 147) at 16 centres in the UK,
Ireland and France with median follow up 51.3 months and 22.9
months respectively. Patients were well matched with no significant
differences in age (median: 23 y vs 27 y), sex, stage (stage 3/4: 81%
vs 83%) and IPS (IPS3+: 74% vs 65%). 51% of eBPDac patients
received only 4 cycles (vs 12% eBPP patients; p < 0.001) reflecting
publication of HD18 trial data. In total, 74% patients achieved
iPET2 Deauville score 3 and 90% achieved PET negative remission
by end of treatment. 77% of eBPDac patients achieved iPET2
Deauville 3 which was statistically similar to the eBPP cohort
(67%; p = 0.181) and matched the 76% iPET D2/3 reported in
HD18. Of 205 patients, 202 are alive and 197 continue in first
remission. Two eBPP patients have relapsed at 13 and 41 months
and the latter died of refractory disease. One eBPDac patient had
primary refractory disease, and three have relapsed at 2, 7 and 24
months. One 56yearold eBPDac patient with high IPS died of
bowel perforation during cycle 1 and one 34yearold with alcoholic
liver disease died 8 months after treatment while in remission.
Toxicity was compared over the first 4 cycles. Mean day 8 (D8) ALT
was similar between the two regimens. Mean D8 neutrophil count
was lower in eBPDac than eBPP patients (1.81 vs 2.45; p = 0.067; G
CSF given D9), however it increased to 5.61 in eBPDac patients
given GCSF from D4. There is a trend toward fewer nonelective
days of inpatient care for eBPDac compared with eBPP (mean 3.74
vs 5.83; p = 0.118), and eBPDac patients received fewer red cell
transfusions compared with eBPP patients (mean 1.93 units vs 4.16
units; p < 0.001). Women aged <35, who completed 4 cycles of
eBPDac/eBPP had a similar rate of return of menstrual cycles (eBPP
22/25; eBPDac 29/29), although eBPDac patients appeared to
restart menstruation earlier post chemotherapy (mean 4.48 months
vs 9.12 months, p = 0.0026). However, this could also reflect the
higher mean chemotherapy cycle number completed by the eBPP
women (5.86 vs 4.60; p < 0.001). The use of Goserelin varied be-
tween centres.
Accepting the limitations of a retrospective study, we suggest that
substituting dacarbazine for procarbazine is unlikely to compromise
the efficacy of eBPP and may have some toxicity benefits. Despite a
predominance of high risk advanced stage patients, with nearly 2
years median follow up we have observed only 2 deaths and 4
SUPPLEMENT ABSTRACTS
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277
progression events from 147 patients treated with eBPDac, sug-
gesting this regimen is highly efficacious in Hodgkin lymphoma.
EA previously submitted to regional or national meetings (up to
1000 attendees) and EHA 2021.
Keywords: Hodgkin lymphoma
Conflicts of interests pertinent to the abstract
A. Santarsieri
Honoraria: Janssen
P. Brice
Other remuneration: Takeda France, Millenium Takeda, BMS
T. F. Menne
Other remuneration: Kite/Gilead, Amgen, Novartis, Celgene, Daiichi
Sankyo, Takeda, Roche, Janssen, Astra Zeneca, Jazz, Pfizer, Bayer,
Kyowa Kirin
W. Osborne
Other remuneration: Roche, Takeda, Pfizer, Servier, Gilead, MSD,
Novartis
K. M. Ardeshna
Other remuneration: Gilead, Celgene
G. P. Collins
Other remuneration: Gilead
K. Cwynarski
Other remuneration: Adienne, Takeda, Roche, Autolus, KITE, Gilead,
Celgene, Atara, Janssen
M. Furtado
Educational grants: Abbvie
S. Iyengar
Other remuneration: Takeda, Janssen, Gilead, Abbvie, Roche
N. MartinezCalle
Other remuneration: Abbvie
P. McKay
Other remuneration: Epizyme
S. K. Nagumantry
Other remuneration: Takeda, Alexion, Abbvie
N. Shah
Other remuneration: Abbvie
B. J. Uttenthal
Other remuneration: Roche, Takeda, Jazz
278
-
SUPPLEMENT ABSTRACTS
A. K. McMillan
Other remuneration: Pfizer, F HoffmanLa Roche Ltd, BMS, Celgene,
Novartis, Gilead, Sandoz, MSD
G. A. Follows
Other remuneration: Janssen, Abbvie, Roche, Astra Zeneca
198 | MATURE RESULTS FROM A PHASE II TRIAL OF
BRENTUXIMAB VEDOTIN PLUS ADRIAMYCIN AND
DACARBAZINE WITHOUT RADIATION IN NONBULKY LIMITED
STAGE CLASSICAL HODGKIN LYMPHOMA
J. S. Abramson
1
, E. M. Bengston
2
, R. Redd
3
, J. A. Barnes
1
,
T. Takvorian
1
, L. Sokol
4
, F. Lansigan
2
, P. Armand
5
, B. Shah
4
,
E. Jacobsen
5
, R. Martignetti
1
, E. Turba
4
, S. R. Metzler
2
, V. Patterson
5
,
A. S. LaCasce
5
, C. M. Bello
4
1
Massachusetts General Hospital, Center for Lymphoma, Boston,
Massachusetts, USA,
2
DartmouthHitchcock Medical Center, Hematology/
Oncology, Lebanon, New Hampshire, USA,
3
DanaFarber Cancer Institute,
Biostatistics, Boston, Massachusetts, USA,
4
Moffitt Cancer Center, He-
matology/Oncology, Tampa, USA,
5
DanaFarber Cancer Institute, Medical
Oncology, Boston, USA
Background: ABVD with or without radiation is standard therapy for
limited stage classical Hodgkin lymphoma (HL), but carries risks of
bleomycin lung injury and radiation toxicity. We previously combined
brentuximab vedotin (BV) with AVD in limited stage HL which
resulted in a high CR rate, but at the cost of increased neutropenic
fever and neuropathy, likely due to overlapping toxicity with BV and
vinblastine; similar findings were observed with BVAVD in advanced
stage HL. We therefore evaluated BV plus AD in nonbulky stage III
HL.
Methods: This is a multicenter single arm phase 2 study. Patients (pts)
received BV 1.2 mg/kg plus standard adriamycin and dacarbazine on
days 1 and 15 of each 28 day cycle. Prophylactic GCSF was not
included. Patients received 4 or 6 cycles based on interim PETCT
performed following cycle 2 (PET pts, defined as Deauville 13,
received 4 cycles, PET+ pts received 6 cycles). Radiation was not
allowed for patients in end of treatment (EOT) CR. The primary
endpoint was complete response rate (CRR) at EOT. A sample size of 34
was required to detect an end of treatment CRR of 95% (compared to
null hypothesis 81%) with 91% power and alpha error of 0.09.
Results: 34 pts were enrolled. Median age was 36 (range 1863).
Stage was IA (3), IB (1), IIA (29) and IIB (1). Risk per the GHSG criteria
was early favorable in 18 (53%) and unfavorable in 16 (47%). The
interim CR rate was 94%; 32 pts received 4 total cycles and 2
received 6 cycles. No pts received consolidative radiation. The pri-
mary endpoint of EOT CRR was 97% (33/34 pts). With a median
followup of 46 months, 31/34 patients remain progressionfree; the
estimated 4year PFS and OS are 88% (95% CI 65,96) and 100%
(95% CI 100,100), respectively. No events have been reported after
30 months. There were no differences in CRR or PFS between early
favorable and unfavorable pts. The most common adverse events of
any grade were nausea (85%), peripheral sensory neuropathy (59%),
fatigue (56%), constipation (41%), alopecia (38%) and neutropenia
(24%). Most toxicities were low grade, with only 5 patients (15%)
experiencing any grade 3 toxicity, and there were no grade 4 or 5
toxicities. Specifically, 2 pts had grade 3 neutropenia, and all other
grade 3 toxicities occurred in 1 pt each. Peripheral neuropathy was
grade 1 in 17 pts and grade 2 in 2 pts. There were no cases of grade 4
neutropenia, and no cases of neutropenic fever.
Conclusions: BVAD for 46 cycles appears highly effective and well
tolerated in both early favorable and early unfavorable nonbulky
limited stage classical HL. Most pts required 4 total cycles. Toxicity
is predominantly low grade and notable for a low incidence of neu-
tropenia, alopecia, and moderatesevere peripheral neuropathy. This
promising regimen avoids bleomycin, vinblastine, radiation and pro-
phylactic GCSF. A phase II trial using this regimen plus nivolumab in
limited stage HL is currently enrolling (ClinicalTrials.gov
NCT03646123).
The research was funded by: Seattle Genetics
Keywords: Hodgkin lymphoma, Chemotherapy, Combination
Therapies
No conflicts of interest pertinent to the abstract.
SUPPLEMENT ABSTRACTS
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279
199 | BRENTUXIMAB VEDOTIN AS CONSOLIDATION
TREATMENT IN PATIENTS WITH STAGE I/II CLASSICAL
HODGKIN'S LYMPHOMA AND A POSITIVE FDGPET AFTER 2
CYCLES OF ABVD: A LYSA PHASE 2 STUDY
T. Gastinne
1
, K. Bouabdallah
2
, H. Moatti
3
, B. Tessoulin
1
, J. M. Shiano
del colella
4
, T. Lamy
5
, O. Casasnovas
6
, C. Borel
7
, A. Stamatoullas
8
,
A. C. Gac
9
, D. Chaoui
10
, P. Feugier
11
, A. Delmer
12
, C. Bonnet
13
, Luc
M. Fornecker
14
, J. Lazarovici
15
, F. Le Bras
16
, H. Ghesquieres
17
,
M. Meignan
18
, A. Traverse Glehen
19
, P. Brice
3
1
University Hospital of Nantes, Hematology, Nantes, France,
2
Hopital
HautLevêque, Centre Hospitalier Regional Universitaire de Bordeaux,
Department of Hematology, Pessac, France,
3
Hôpital saint Louis APHP,
Université Paris 7, Department of Oncohaematology, Paris, France,
4
Institut PaoliCalmettes, AixMarseille Université, Haematology Depart-
ment, Marseille, France,
5
Rennes University Hospital, Department of
Clinical Hematology, MICA Research Unit, Rennes, France,
6
University
Hospital F Mitterrand and INSERM 1231, Department of Haematology,
Dijon, France,
7
IUCTOncopole, CHU Toulouse, Department of Haema-
tology, Toulouse, France,
8
Centre Henri Becquerel, Department of
FIGURE 1
280
-
SUPPLEMENT ABSTRACTS
Haematology, U918, Rouen, France,
9
Centre Hospitalier Universitaire de
Caen, Institut d'hématologie de BasseNormandie , Caen, France,
10
Centre
Hospitalier d'Argenteuil, Department of Hematology, Argenteuil, France,
11
Nancy University Hospital, Department of Clinical Hematology, INSERM
1256, Nancy, France,
12
University Hospital of Reims, Department of
Haematology, Reims, France,
13
CHU Liège, Liège Université, Campus
Universitaire de Sart Tilman, Clinical Hematology Unit, Liège, Belgium,
14
Strasbourg University Hospital, Department of Clinical Hematology,
Strasbourg, France,
15
Institut Gustave Roussy, Département des In-
novations Thérapeutiques et Essais Précoces, Villejuif, France,
16
CHU
Henri Mondor, Department of Hematology, Creteil, France,
17
Hospices
Civils de Lyon, Centre Hospitalier LyonSud and Université Claude Ber-
nard Lyon1, Department of Haematology, Lyon, France,
18
Hôpital H
Mondor, LYSA Imaging, Creteil, France,
19
Centre Hospitalier LyonSud,
Hospices Civils de Lyon, Pathology Department, cedex, France, Lyon,
France
Brentuximab vedotin (BV) as consolidation treatment in patients with
stage I/II classical Hodgkin's lymphoma and a positive FDGPET after
2 cycles (PET2) of ABVD: a LYSA phase 2 study.
Introduction: Earlystage classical Hodgkin lymphoma (cHL) is highly
curable with chemotherapy and radiotherapy (RT). However, patients
with positive interim PET2 have poorer prognosis and require
treatment intensification. Indeed, the H10 trial (André et al., 2017)
showed that escalated BEACOPP (BEACOPPesc) plus RT improves
5year PFS in PET2 positive patients treated with ABVD. The main
objective of the present study (NCT02298283) was to investigate the
benefit of a consolidation with Brentuximab vedotin (BV) in newly
diagnosed early stage HL patients with insufficient response ac-
cording to TEP after 2 cycles.
Patients and methods: The BRAPP2 trial is a multicentric, openlabel,
single arm phase II trial. All Patients aged from 18 to 65 years, with
an Ann Arbor clinical stage I or II cHL, PET2 Deauville score 4 & 5
after 2 courses of ABVD and without progressive disease were
eligible for the study. After inclusion, patients received 2 courses of
BEACOPPesc (socalled induction) followed unless disease progres-
sion, by 30 Gy IFRT and then BV consolidation. BV (1.8 mg/kg) was
started at least 4 weeks and up to 6 weeks after RT and was given
every 3 weeks for 8 cycles. The BRAPP2 was designed to detect an
improvement of PFS at 2 years from 70% (null hypothesis) to 85%
(alternative hypothesis) assuming an 80% power at a 2sided alpha
(type I error) of 5%.
Results: From 04/2015 to 04/2018, 48 patients were included of
whom 41 patients started BV consolidation (efficacy and safety set),
and 35 received the full 8 cycles of BV (Figure 1). A total of 56
adverse events (AEs) were reported during the study in 26 patients
(63.4%). Most frequent AEs were neurological with 12 patients
(29.3%) having experienced a grade 2 peripheral neuropathy, all
related to BV and leading to treatment discontinuation in 2 cases.
Febrile neutropenia occurred in 12.2% of patients, and was reported
during induction period. No fatal AEs were reported. According to
Cheson 2007 criteria, 34 patients (87.2%, 95%CI [72.6%; 95.7%])
achieved CR, evaluated after complete treatment for 85% patients.
With a median followup duration of 3.1 years (95%CI = [2.6; 3.3]), 4
out of 41 (9.8%) patients progressed. The 2year PFS was 90.0%
(95%CI [75.5%; 96.1%]). One patient died, due to progression
(aggressive Bcell lymphoma). The 2year OS was 97.5% (95%CI
[83.5%; 99.6%]). According to statistical study design, the null hy-
pothesis is rejected.
Conclusion: BEACOPPesc plus RT followed by BV consolidation for
PET2 positive early stage cHL provides high CR rate and prolonged
PFS with limited and manageable toxicities. BV consolidation is thus
an attractive option in this group of patients while there is still a
room for improvement to reduce progression during the induction
phase.
Keywords: Hodgkin lymphoma, Therapeutics and Clinical Trials in
Lymphoma Other
Conflicts of interests pertinent to the abstract
T. Gastinne
Consultant or advisory role: Gilead, Janssen, Takeda
Educational grants: Gilead, Roche
200 | OUTCOMES AFTER INITIAL REFUSAL OF CURATIVE
TREATMENT IN PATIENTS WITH HODGKIN LYMPHOMA IN
BRITISH COLUMBIA
M. Chahal
1
, A. Jiang
2
, A. Hayden
3
, K. Savage
4
, D. Villa
4
, D. Scott
4
,
A. Gerrie
4
, A. Lo
5
, M. Chan
5
, T. Pickles
5
, J. Connors
4
, L. Sehn
4
,
C. Freeman
4
1
BC Cancer, Medical Oncology, Vancouver, Canada,
2
British Columbia
Cancer Research Centre, Biostatistics, Vancouver, Canada,
3
BC Cancer,
Medical Oncology, Surrey , Canada,
4
BC Cancer, Centre for Lymphoid
Cancer and Division of Medical Oncology, Vancouver, Canada,
5
BC
Cancer, Division of Radiation Oncology, Vancouver, Canada
Background: Classical Hodgkin lymphoma (cHL) is considered a
highly curable cancer. With standard combination chemotherapy
regimens, longterm survival exceeds 95% for limitedstage and 85%
for advancedstage patients. Despite these excellent outcomes some
patients delay or decline conventional treatment for cHL. We
retrospectively assessed the impact of initial treatment refusal on
outcomes of patients with cHL in British Columbia (BC).
Methods: Using the BC Cancer Lymphoid Cancer Database, we
identified all patients aged 1870 diagnosed between 1
st
Jan 1999
31
st
Dec 2020 that had documented treatment refusal at initial
presentation (‘refusers’ defined as not receiving or delaying treat-
ment >16 weeks). We identified a control cohort (min. 3 controls/
refuser) treated within 8 weeks of diagnosis, matched for age, stage,
diagnosis date within 3 years, and blinded for outcome. All patients
had centrally reviewed biopsies and were treated with ABVD or
ABVDlike regimens +/ radiotherapy if appropriate. Patient and
disease characteristics at baseline and at time of treatment were
analyzed with Chisquared test and oneway ANOVA test. The
KaplanMeier method was used to assess progressionfree survival
SUPPLEMENT ABSTRACTS
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281
(PFS) and overall survival (OS), and statistical significance between
groups was determined using the logrank test.
Results: We identified a cohort of 15 patients who initially refused
treatment and 47 matched controls. The control cohort was well
matched, with no statistically significant differences in baseline char-
acteristics (age, sex, Ann Arbor stage, B symptoms, International
Prognostic Score (IPS) score, ECOG PS, and disease bulk) between
groups. The most common reason for initial treatment refusal was to
pursue alternative therapy (73%). 13 of 15 refusers eventually
accepted treatment (mean time to treatment 76 weeks [range 26214]
vs. 5 weeks [range 18] for controls, p < 0.001). At time of treatment,
the proportion of refusers with advancedstage disease increased from
20% to 62% (p = 0.03) and had an associated alteration of treatment
plan, and 62% of patients developed higher risk disease with increased
IPS score (p = 0.02). At median followup of 5 years (0.421 years) for
all living patients, estimated 5year PFS was 65% vs 84%, and 5year
OS was 93% vs 98% for refusers and controls respectively. With
extended follow up, 13% of refusers (1 late death at 8 years) compared
to only 4% of controls died of cHL specifically.
Conclusions: This study highlights the impact of treatment refusal in
this highly curable malignancy. Initial refusal of treatment is associ-
ated with progression of stage, worsening prognostic score, escala-
tion to more prolonged treatment than required at diagnosis, and
increased risk of death from cHL. This analysis may help to provide
guidance to counselling physicians, as well as inform patients who
may be considering alternatives to standard of care for cHL.
EA previously submitted to ASCO 2021.
Keywords: Hodgkin lymphoma
Conflicts of interests pertinent to the abstract
K. Savage
Consultant or advisory role: Seattle Genetics, BristolMyers Squibb,
Merck, Servier, Abbvie, Gilead Sciences, AstraZeneca
Honoraria: Seattle Genetics, BristolMyers Squibb, Merck, Abbvie,
Gilead Sciences, AstraZeneca, Kyowa Kirin, Novartis, Novartis Can-
ada Pharmaceuticals Inc
Research funding: Roche, BristolMyers Squibb
Educational grants: Seattle Genetics
Other remuneration: Beigene
D. Villa
Consultant or advisory role: Roche, Janssen, Lundbeck Canada,
Seattle Genetics, Gilead Sciences, Acerta Pharma/AstraZeneca, Cel-
gene, Abbvie, NanoString Technologies
Honoraria: Roche, Janssen, Lundbeck Canada, Seattle Genetics,
Gilead Sciences, Acerta Pharma/AstraZeneca, Celgene, Merck,
NanoString Technologies, Abbvie
Research funding: Roche
Educational grants: Roche, Janssen, Ludbeck Canada, Acerta Pharma
D. Scott
Consultant or advisory role: Celgene, Janssen, Sbbvie, AstraZeneca
Research funding: Janssen, Roche/Genetech, NanoString Technologies
A. Gerrie
Consultant or advisory role: Janssen, Abbvie, AstraZeneca, Sandoz
Honoraria: Janssen, Abbvie
Research funding: Abbvie, Roche Canada, Janssen, AstraZeneca
Educational grants: Janssen
T. Pickles
Honoraria: Abbvie, TerSera
Research funding: Astellas Oncology
L. Sehn
Consultant or advisory role: Celgene, Abbvie, Seattle Genetics, TG
Therapeutics, Janssen, Amgen, Roche, Gilead Sciences, Lundbeck,
apobiologix, Kite Pharma, Merck, Takeda, AstraZeneca, Acerta
Pharma, SandozNovartis, MorphoSys, Genmab, Verastem
Honoraria: Amgen, Apobiologix, Abbvie, Celgene, Gilead Sciences,
Janssen, Kite Pharma, Lundbeck, Merck, Roche, Seattle Genetics,
Takeda, Teva, TG Therapeutics, Karyopharm, AstraZeneca, Acerta
Pharma, Morphosys, Incyte, Debiopharm, SandozNovartis, Vera-
stem, Genmab
Research funding: Roche/Genetech, Teva
C. Freeman
Honoraria: BMSi, Seattle Genetics, Janssen, Amgen, Celgene, Sanofi,
Abbvie
Educational grants: Roche, Teva
201 | PROGNOSTIC FACTORS IN ELDERLY PATIENTS WITH
CLASSICAL HODGKIN LYMPHOMA A JOINT ANALYSIS OF TWO
CLINICAL DATABASES
M. Fehr*
1
, N. Lang*
2
, L. Rubio
3
, S. Güsewell
4
, A. J. Templeton
5
,
S. Aeppli
1
, R. Tsang
6
, D. Hodgson
6
, A. Moccia
7
, M. Bargetzi
8
,
C. Caspar
9
, D. M. A. Brülisauer
10
, M. Ebnöther
5
, N. Fischer
11
,
A. Prica
6
, V. Kukreti
6
, G. Ghilardi
12
, F. Krasniqi
13
, U. J. Mey
14
,
W. Mingrone
15
, U. Novak
10
, P. Richter
14
, R. Kridel
6
, D. Rodin
16
,
M. Rütti
17
, A. Schmidt
18
, F. Stenner
13
, M. Voegeli
19
, T. Zander
20
,
M. Crump
6
, F. Hitz*
1
, J. Kuruvilla*
6
1
Cantonal Hospital St. Gallen, Medical Oncology and Haematology,
St. Gallen, Switzerland,
2
Hôpitaux Universitaires Genève, Department of
Oncology, Genève, Switzerland,
3
Manchester Royal Infirmary,
Haematology, Manchester, UK,
4
Cantonal Hospital St. Gallen, Clinical
Trials Unit, St. Gallen, Switzerland,
5
Claraspital Basel, Oncology and
Haematology, Basel, Switzerland,
6
Princess Margaret Cancer Centre,
Medical Oncology and Haematology, Toronto, Canada,
7
Oncology
Institute of Southern Switzerland, Department of Medical Oncology,
Bellinzona, Switzerland,
8
Cantonal Hospital Aarau, Haematology, Aarau,
Switzerland,
9
Cantonal Hospital Baden, Oncology und Haematology,
Baden, Switzerland,
10
University Hospital Bern, Medical Oncology, Bern,
Switzerland,
11
Cantonal Hospital Winterthur, Medical Oncology and
Haematology, Winterthur, Switzerland,
12
Oncology Institute of Southern
Switzerland, Haematology, Bellinzona, Switzerland,
13
University Hospital
282
-
SUPPLEMENT ABSTRACTS
Basel, Oncology, Basel, Switzerland,
14
Cantonal Hospital Grisons,
Oncology and Haematology, Chur, Switzerland,
15
Cantonal Hospital
Olten, Centre for Oncology, Olten, Switzerland,
16
Princess Margaret
Cancer Centre, Radiation Oncology, Toronto, Switzerland,
17
Hospital Wil,
Medicine, Wil, Switzerland,
18
Stadtspital Triemli, Medical Oncology und
Haematology, Zürich, Switzerland,
19
Cantonal Hospital Baselland,
Oncology and Haematology, Liestal, Switzerland,
20
Cantonal Hospital
Luzern, Medical Oncology, Luzern, Switzerland
Background: Prognostic factors for elderly patients 60 years of
age with classical Hodgkin Lymphoma (cHL) are not well estab-
lished. Previous studies have shown that patientrelated factors
such as comorbidities and performance status (ECOGPS), disease
specific factors (extranodal disease) and markers of host inflam-
mation (e.g. neutrophillymphocyte ratio [NLR]) can be associated
with clinical outcomes in elderly patients with cHL. Therefore
the aim of this study was to evaluate the association of cause
specific survival (CSS) and overall survival (OS) with age, stage,
Charlson comorbidity index (CCI) and these additional patient and
diseaserelated factors in a large dataset of elderly patients
with cHL.
Method: Joint analysis of Princess Margaret and Swiss elderly cHL
databases of patients from 2000 to 2018. Main inclusion criteria
were age 60 years, diagnosis of cHL, treatment with chemotherapy
(CT) or combined modality therapy (CMT). Patients with nodular
lymphocyte predominate HL (NLPHL) and treated with radio-
therapy alone were excluded. Univariable and multivariable models
were applied.
Results: Overall, 309 patients from 1 Canadian (n = 72) and 15 Swiss
centers (n = 237) were included. Excluded were 10 patients with RT
alone and 11 with NLPHL. Median age was 70 years (range 60 91),
median CCI was 7 (4 16), 17.2% of patients had stage I, 30.1 %
stage II, 29.9% stage III and 28.5% stage IV cHL. Overall, 5years
OS was 62.4% [95%CI 56.8 68.5] and 5years CSS was 82.6%
[78.1 87.4]. 189 (61.2%) patients were treated with CT alone, 120
(38.8.%) patients with CMT; 240 (77.7%) patients received
anthracyclinecontaining CT, 69 (22.3%) patients received non
anthracyclinecontaining CT.
In univariable analysis, age, stage, CCI, NLR and ECOGPS showed
significant associations with both endpoints, all pvalues < 0.01.
Results of the multivariable analysis are demonstrated in table1.
Conclusion: In this large, international cohort of patients aged 60
years with cHL age, CCI and ECOGPS are independent factors
associated with OS. Age and stage are independently associated with
causespecific survival while NLR and extranodal disease are not
independently associated with clinical outcomes.
*contributed equally
Keywords: Diagnostic and Prognostic Biomarkers, Hodgkin lymphoma
No conflicts of interest pertinent to the abstract.
202 | MTV, TLG AND SUV MAX AS PROMISING PARAMETERS
TO PREDICT EARLY RESPONSE IN PATIENTS WITH HL TREATED
WITH ABVD. A RETROSPECTIVE SUBANALYSIS OF THE GATLA
LH05 TRIAL
J. Iorio
1
, M. Eleta
1
, V. Plates
1
, L. Fiad
1
, M. Riddick
1
, A. Pavlovsky
1
1
IMAXE, Imagenes, CIUDAD DE BUENOS AIRES RECOLETA, Argentina
Introduction: Increased tumor burden is associated with inferior
outcomes in different lymphoma subtypes. Surrogates of tumor
burden, such as the maximum tumor dimension of the “bulkiest”
lesion on computed tomography (CT) have been used as a prognostic
index for many years. Recently, the total metabolic tumor volume
(MTV), tumor lesion glycolysis (TLG) and SUV max in basal PETCT
have emerged as promising and robust biomarkers of outcomes in
patients with Hodgkin's Lymphoma (HL). Interim PETCT is also a
wellestablished prognostic factor for PFS in HL. We aim to identify
quantitive parameters from basal PETCT to predict early response in
interim PET (iPET) as a surrogate of PFS.
Methods: We performed a retrospective analysis of the database of
562 patients with HL who were enrolled between November 2008
and March 2020 in the GATLALH05 trial. We searched for patients
who underwent a basal PETCT at the same PET center; MTV was
computed using 41% maximum standardize uptake value method:
TLG and SUVmax were derived. After 3 cycles of ABVD all patients
underwent an iPET. In this published trial patients with a negative
iPET had a PFS of 90% vs 65% in patients with iPET positive. Mann
Whitney test was performed to analyze difference of MTV, TLG and
SUV max, between PET positive and PET negative cohorts.
TABLE 1 Multivariable cox models: Hazard ratios with 95% CI and pvalues from Wald tests
Overall survival Causespecific survival
HR (95% CI) pvalue HR (95% CI) pvalue
Age (3 groups, per decennium) 1.85 (1.412.45) <0.001 1.90 (1.232.92) 0.004
Stage (I, II, III, IV, per level) 1.26 (0.991.59) 0.056 2.15 (1.413.28) <0.001
Charlson comorbidity index (3 groups: 46, 78, 9+, per level) 1.53 (1.181.99) 0.001 1.24 (0.821.89) 0.314
NLR (logtransformed) 1.06 (0.841.34) 0.629 1.04 (0.741.46) 0.825
ECOG Performance Status (3 groups: 0, 1, 24, per level) 1.39 (1.071.82) 0.015 1.26 (0.821.93) 0.294
Extranodal involvement (yes vs. no) 1.15 (0.731.79) 0.548 0.59 (0.301.19) 0.143
SUPPLEMENT ABSTRACTS
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283
Results: Of the total population, 64 patients had complete informa-
tion for this analysis, 40 (62.5%) patients had iPET negative, and 24
(37.5 %) iPET positive.
According to positive vs negative interim PET we identified the
following difference in basal PET. (Table 1):
In this retrospective analysis, difference between the distribution of
the baseline values of MTV and TLG variables, was statistically sig-
nificant between the group of patients that achieved an IPET negative
vs those who had IPET positive (p = 0.001 and p = 0.005 respectively).
Finally, SUV max at baseline PET did not show significant differences
between patients who did or did not achieve an iPET negative (p = 0.1).
Conclusions: In this explorative study, a high total MTV and TLG at
baseline PET are robust parameters to predict early response in the
interim PET. In this analysis we demonstrate the association of high
basal MTV and TLG as a predictor of early metabolic response, a
surrogate of PFS. This contributes to the growing evidence of the
importance of these values to predict outcome.
SUV max did not show correlation with early metabolic response.
A prospective clinical trial to reevaluate these important findings in a
larger group of patients, with an attempt to determine a reliable cut
off value in MTV and TLG is being planned.
Keywords: Hodgkin lymphoma
No conflicts of interest pertinent to the abstract.
203 | BASELINE MAXIMUM TUMOUR DIAMETER IS
ASSOCIATED WITH EVENTFREE SURVIVAL FOR PETNEGATIVE
PATIENTS WITH LIMITEDSTAGE HODGKIN LYMPHOMA:
ANALYSIS OF THE H10 AND RAPID TRIALS
E. H. Phillips
1
, N. Counsell
2
, T. Illidge
1
, M. Andre
3
, I. Aurer
4
, V.
Fiaccadori
5
, C. Fortpied
6
, A. Neven
6
, M. Federico
7
, L. CliftonHadley
2
,
S. Barrington
8
, J. Raemaekers
9
, J. Radford
1
1
University of Manchester, The Christie NHS Foundation Trust and NIHR
Manchester Biomedical Research Centre, Manchester, UK,
2
University
College London, Cancer Research UK and UCL Cancer Trials Centre, London,
UK,
3
CHU UCL Namur, Department of Haematology, Yvoir, Belgium,
4
University Hospital Centre Zagreb, Division of Hematology, Department of
Internal Medicine, Zagreb, Croatia,
5
University College London, Cancer
Institute, London, UK,
6
European Organisation for Research and Treatment
of Cancer, EORTC Headquarters, Brussels, Belgium,
7
University of Modena
and Reggio Emilia, CHIMOMO Department, Modena, Italy,
8
King's College
London and King's Health Partners, King's College London and Guy's and St
Thomas' PET Centre, School of Biomedical Engineering and Imaging
Sciences, London, UK,
9
Radboud University Medical Center, Department of
Haematology, Nijmegen, Netherlands
Introduction: Trials evaluating responseadapted use of radiotherapy
(RT) in limitedstage Hodgkin lymphoma (LSHL) have shown that the
negative predictive value of PET is suboptimal. Additional biomarkers
are needed to facilitate a riskadapted approach. In the UK NCRI
RAPID trial, baseline maximum tumour diameter (MTD) was
associated with eventfree survival (EFS) for LSHL patients (pts)
who achieved complete metabolic response (CMR; Illidge et al,
Blood Advances 2020). The aim of this analysis was to validate these
findings in an independent cohort from the EORTC/LYSA/FIL H10 trial.
Methods: H10 recruited pts with stage I/II HL. Pts with CMR after 2x
ABVD received either chemotherapy alone (C) with 46x ABVD (N =
540), or combined modality therapy (C + RT) with 34x ABVD plus
RT (N = 1024). RAPID recruited pts with stage I/II HL, without
mediastinal bulk or B symptoms. Pts with CMR after 3x ABVD were
randomised to no further therapy (C; N = 211) or RT (C + RT; N =
208). Baseline MTD (in cm) was assessed by CT and locally reported.
We describe the association with EFS, defined as progression or HL
related death, for pts with CMR, adjusted for treatment group and
stratified by trial (in pooled analyses).
Results: For H10 pts that were RAPIDeligible (no B symptoms or
mediastinal bulk), we found a clear association between MTD and
EFS (N = 859; HR = 1.22, 95% CI: 1.071.38, p < 0.01), similar to that
observed in RAPID (HR = 1.19, 95% CI: 1.021.39, p = 0.02). Results
were consistent when adjusted for number of ABVD cycles and
EORTC risk stratification. There was no evidence of an association
between MTD and EFS for RAPIDineligible H10 pts (N = 672; HR =
1.03, 95% CI: 0.961.11, p = 0.37).
For RAPIDeligible pts receiving C, there was a similar associa-
tion between MTD and EFS in both RAPID (HR = 1.20, 95% CI: 0.99
1.44, p = 0.06) and H10 (N = 303; HR = 1.19, 95% CI: 1.011.40, p =
0.03). In a pooled analysis, the risk of relapse was on a continuum
with increasing MTD (N = 514; HR = 1.19, 95% CI: 1.011.35, p <
TABLE 1 Baseline values of MTV, TLG and SUV max
Basal MTV Median Mean Standard deviation
PET + 167.27 ml. 263.49 ml. 339.86 ml.
PET 67.14 ml. 116.93 ml. 150.87 ml.
Basal TLG
PET + 584.98 ml. 890.44 ml. 898.90ml.
PET 225.53 ml. 453.78 ml. 785.61 ml.
Basal SUV
PET + 12.37 ml. 13.42 ml. 6.08 ml.
PET 10.77 ml. 11.01 ml. 6.54 ml.
284
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SUPPLEMENT ABSTRACTS
0.01), with no clear MTD threshold above which we could identify a
marked difference in EFS. An MTD threshold of 5cm (AUC = 60.0%)
performed marginally better than 4cm, 3cm and 6cm (AUC = 59.2%,
58.5% and 56.7%, respectively) in timedependent receiver operating
characteristic curve analyses.
In an exploratory, pooled analysis of RAPIDeligible pts treated
with C+RT, MTD was associated with EFS (N = 764; HR = 1.24, 95%
CI: 1.051.46, p < 0.01). With only 20 events in this group, it was not
possible to evaluate MTD thresholds, and EFS rates were high irre-
spective of MTD (Figure).
Conclusions: This validation study confirms the association between
baseline MTD and relapse risk for LSHL pts without B symptoms or
mediastinal bulk who achieve CMR, in an independent cohort. Out-
comes for pts with high MTD treated with C alone were suboptimal.
These findings inform discussion of risk for personalised application
of RT in LSHL and the design of future trials.
Keywords: Imaging and Early Detection Other, Hodgkin lymphoma
No conflicts of interest pertinent to the abstract.
204 | SARCOPENIAIS AN INDEPENDENT PROGNOSTIC FACTOR
IN ELDERLY MALE PATIENTS WITH CLASSICAL HODGKIN
LYMPHOMA: RESULTS FROM A MULTICENTER EXPERIENCE
V. R. Zilioli
1
, D. Albano
2
, A. Arcari
3
, F. Merli
4
, A. Coppola
5
, G. Besutti
6
,
L. Marcheselli
7
, D. Gramegna
8
, C. Muzi
1
, M. Manicone
6
, M. Camalori
5
,
P. Ciammella
9
, G. Colloca
10
, A. Tucci
8
1
ASST Grande Ospedale Metropolitano Niguarda, Hematology, Milan, Italy,
2
ASST Spedali Civili, Nuclear Medicine, Brescia, Italy,
3
Ospedale Guglielmo
da Saliceto, Hematology, Piacenza, Italy,
4
Azienda USL IRCCS di Reggio
Emilia, Hematology, Reggio Emilia, Italy,
5
ASST Grande Ospedale
Metropolitano Niguarda, Radiology, Milan, Italy,
6
University of Modena and
Figure:
EFS according to treatment group and MTD for patients achieving in A) RAPID and B) H10
SUPPLEMENT ABSTRACTS
-
285
Reggio Emilia, Clinical and Experimental PhD program, Modena, Italy,
7
Fondazione Italiana Linfomi Onlus, Trial Office Modena, Modena, Italy,
8
ASST Spedali Civili, Hematology, Brescia, Italy,
9
Azienda USL IRCCS di
Reggio Emilia, Radiotherapy, Reggio Emilia, Italy,
10
Fondazione Policlinico
Universitario A. Gemelli, IRCCS, Geriatrics, Rome, Italy
Introduction: Classical Hodgkin Lymphoma in the elderly (ecHL) is a
rare disease with dismal prognosis and no standard treatment. In
elderly lymphoma patients (pts) functional status evaluation helps
define different prognostic subgroups and may be useful to design
appropriate treatments. Sarcopenia has been associated with worse
survival in various solid tumors, but its impact in ecHL is unknown.
The aim of this retrospective multicenter study was to investigate the
prognostic role of sarcopenia in ecHL.
Methods: We retrospectively analyzed 65 years old ecHL pts
treated at 4 participating centers, who performed a baseline
comprehensive geriatric assessment (CGA) and highdose computed
tomography (CT) or positron emission tomography/CT (PET/CT)
before any treatment. Sarcopenia was measured as skeletal muscle
index (SMI, cm
2
/m
2
) by the analysis of high dose CT or lowdose PET/
CT images at the L3 level. The specific cutoffs for the SMI were
determined by receiver operator curve (ROC) analysis and compared
with those studied in Diffuse Large B Cell Lymphoma (DLBCL) pts
(Lanic et al, Leuk Lymphoma 2014; Nakamura et al, Ann Hematol
2015). Survival functions (Progression Free Survival, PFS; Overall
Survival, OS) were calculated for the whole population and for
different subgroups defined as per different sarcopenia cutoff levels.
Results: One hundred and fiftyfour pts (median age 71y, 76 females)
were included in the study. The median L3SMI was 42 cm2/m2. The
specific cutoff derived in our male population was 45 cm2/m2; using
this cutoff, 27 male pts (35%) were defined as sarcopenic. After a
median followup of 5.9 years, the overall 5year PFS and OS rates
were 53% and 65%, respectively, and were significantly shorter in
sarcopenic males compared to nonsarcopenic (PFS 31% vs 61%, p =
0.008; OS 51% vs 74%, p = 0.042) [Figure 1]. Applying DLBCLderived
sarcopenic thresholds, there were no significant differences between
sarcopenic and nonsarcopenic pts for both PFS and OS, with a sole
exception of a significant reduced PFS in sarcopenic male pts using
Namakuracut off. The CGAdetermined frail functional status was an
independent adverse prognostic factor for both female and male pts.
Conclusions: Baseline evaluation of sarcopenia through radiological
examinations performed for ecHL staging may help define a pro-
portion of male pts with unfavorable outcome with current treatment
strategies. Also the functional status evaluation could allow to
identify a frail subgroup of pts with worse outcome. Prospective
studies are warranted to better define the effective role and utility of
this approach in the setting of ecHL.
Keywords: Hodgkin lymphoma
No conflicts of interest pertinent to the abstract.
205 | GUT MICROBIOTA ROLE IN RESPONSE TO CHECKPOINT
INHIBITOR TREATMENT IN PATIENTS WITH RELAPSED/
REFRACTORY BCELL HODGKIN LYMPHOMA: AN INTERIM
ANALYSIS FROM MICROLINF STUDY
B. Casadei
1
, S. Guadagnuolo
1
, M. Barone
2
, S. Turroni
3
, L. Argnani
1
,
P. Brigidi
2
, P. L. Zinzani
1
1
IRCCS Azienda OspedalieroUniversitaria di Bologna Istituto di Emato-
logia “Seràgnoli”, and Dipartimento di Medicina Specialistica, Diagnostica
e Sperimentale Università di Bologna, n/a, Bologna, Italy,
2
University of
FIGURE 1 OS and PFS according to sarcopenic status defined by our specific population cutoff [<45 cm
2
/m
2
] in male patients
286
-
SUPPLEMENT ABSTRACTS
SUPPLEMENT ABSTRACTS
-
287
Bologna, Department of Medical and Surgical Sciences, Bologna, Italy,
3
University of Bologna, Department of Pharmacy and Biotechnology,
Bologna, Italy
Background: Singleagent monoclonal antibodies targeting the im-
mune checkpoint PD1 (programmed death 1) are an efficient and
safe therapeutic option in patients with relapsed/refractory Bcell
lymphoma. However, many patients progress or lose response to
antiPD1. Recent studies have highlighted the role of the gut
microbiota (GM) in influencing the response to chemo
immunotherapeutic agents. Here we hypothesize that the GM dy-
namics in Bcell lymphoma patients during antiPD1 therapy corre-
late with treatment response.
Methods: From December 2017 to December 2020 we enrolled 17
patients (12 with classical Hodgkin lymphoma [cHL] and 5 with pri-
mary mediastinal Bcell lymphoma) treated with antiPD1 due to
relapsed/refractory disease. Feces were collected at baseline, before
each therapy cycle, at response assessment (during both therapeutic
course and followup) and for grade 2 adverse events, and profiled
through Illumina sequencing. At each time point, patients compiled a
7day weighted food intake record that was analyzed by MètaDieta
(METEDA).
Results: We report the results of the first 6 patients enrolled, all
affected by cHL. Median age was 31 years (range 2671), 5 patients
were female. Five patients were refractory to the last therapy, with a
median of previous treatments of 3 (range 35). All patients dis-
continued treatment: 3 due to disease progression; 2 achieved
complete remission and interrupted to consolidate with autologous
stem cell transplantation; the last due to grade 3 adverse event
despite partial remission. The median number of antiPD1 cycles was
15 (range 718).
The baseline GM separated from that of age/gendermatched
healthy controls, being enriched in the pathobiont Collinsella while
depleted of healthassociated taxa, e.g. Faecalibacterium, Rumino-
coccus, Coprococcus and Roseburia (p < 0.05; Figure 1A). The GM
dynamics along antiPD1 treatment were distinct in relation to the
therapeutic response, with greater temporal variability of alpha di-
versity in responders (Figure 1B). The latter consumed more fat and
fewer carbohydrates.
Conclusions: The GM of patients with relapsed/refractory Bcell
Hodgkin lymphoma is dysbiotic and shows distinct trajectories
during antiPD1 treatment, closely related to the therapeutic
response.
Keywords: Diagnostic and Prognostic Biomarkers, Immunotherapy
No conflicts of interest pertinent to the abstract.
206 | CHARACTERIZATION OF CANCER ASSOCIATED
FIBROBLASTS IN CLASSICAL HODGKIN LYMPHOMA
K. Karihtala
1
, S.K. Leivonen
1
, M.L. KarjalainenLindsberg
2
,
A. Östman
3
, T. Pellinen
4
, S. Leppä
1
1
University of Helsinki, Faculty of Medicine, Research Program Unit,
Applied Tumor Genomics, Helsinki, Finland,
2
Helsinki University Hospital,
Department of Pathology, Helsinki, Finland,
3
Karolinska Institutet,
Department of OncologyPathology, Stockholm, Sweden,
4
Institute for
Molecular Medicine Finland, (FIMM), Helsinki, Finland
Introduction: Cancerassociated fibroblasts (CAFs) are a heteroge-
neous cell population with diverse functions. They constitute an
important stromal component of the tumor microenvironment (TME),
are in close crosstalk with tumor cells, regulate immune responses and
promote tumor progression. In classical Hodgkin lymphoma (cHL), the
role of CAFs is largely undefined. Here, we aimed to characterize
distinct CAF subsets from diagnostic cHL samples and associate the
findings with other TME cells, immune response genes, clinical char-
acteristics and outcome of patients with previously untreated cHL.
Methods: CAFs as well as tumor associated macrophages, T cells and
different checkpoint molecules were phenotyped from diagnostic
131 cHL samples using multiplex immunohistochemistry (mIHC) with
digital image analysis. Plateletderived growth factor receptor
(PDGFR) α and β, fibroblastactivation protein (FAP) and α‐smooth
muscle actin (α‐SMA) were utilized as markers for CAFs. Nanostring
based data from a 770gene immune panel was used to correlate
CAF proportions with gene expression.
Results: Median age of the patients was 30 years (range 1683), 78%
had nodular sclerosis subtype and 56% advanced stage. Primary
treatment (85%) was mostly doxorubicin, bleomycin, vinblastine,
dacarbazine (ABVD), and in limited stage disease, ABVD in combi-
nation with radiotherapy. At the median followup time of 55 months
(range 7229), 22% of the patients relapsed and 8% died. Fiveyear
freedom from treatment failure (FFTF) was 79% and overall sur-
vival (OS) 91%.
From all cells in the cHL TME, 20% were PDGFRβ (range 0.2
92%), 19% FAP (range 088%), 16% α‐SMA (range 256%), and 1%
PDGFRα (range 0.158%) positive. In Cox univariate analysis, high
proportion of FAP
+
cells associated with inferior FFTF (HR 1.25, 95%
CI 1.01.5, P = 0.020), also after adjustment by age.
In a small cHL subgroup, FAP
+
and PDGFRα
+
markers were co
localized. Interestingly, PDGFRα
+
FAP
+
double positive phenotype
translated to better FFTF and OS (5y FFTF 100 % vs. 76%, P = 0.035;
5y OS 100% vs. 90%, P = 0.270). Patient demographics were equally
distributed between the subgroups. According to the pathway analysis,
focal adhesion and extracellular matrix genes were enriched in the
cHLs displaying PDGFRα
+
FAP
+
phenotype. PDGFRα
+
FAP
+
pheno-
type associated positively with high proportion of tumor associated
macrophages (P = 0.026), and negatively with T cells (P = 0.006) and
checkpoint molecule indoleamine 2,3 dioxygenase 1 (IDO1)
+
cells (P =
0.002). In addition, IDO1 mRNA levels correlated inversely with the
proportion of PDGFRα
+
FAP
+
cells (ρ = 0.530, P < 0.001).
Conclusions: Our data demonstrate that CAF subsets are clinically
relevant in cHL, and suggest that a newly identified subset of
PDGFRα
+
FAP
+
CAFs has prognostic impact on survival in cHL patients.
The research was funded by: grants from the Academy of Finland (S.
L.), Finnish Cancer Organizations (S.L.), Sigrid Juselius Foundation (S.
288
-
SUPPLEMENT ABSTRACTS
L.), University of Helsinki (S.L.), Helsinki University Hospital (S.L.),
University of Helsinki, Doctoral Programme in Clinical Research (K.
K.), Finnish Society for Oncology (K.K.) and Orion Research Foun-
dation (K.K.)
Keywords: Tumor Biology and Heterogeneity, Hodgkin lymphoma
Conflicts of interests pertinent to the abstract
K. Karihtala
Educational grants: Gilead
S. Leppä
Consultant or advisory role: JanssenCilag, Novartis, Roche, Takeda,
Merck
Honoraria: Roche, Takeda, Merck, Celgene
Research funding: JanssenCilag, Roche, Takeda, Bayer, Celgene
207 | TRACKING CLONAL HEMATOPOIESIS IN PATIENTS
WITH CLASSICAL HODGKIN'S LYMPHOMA
*A. Marra (cofirst author)
1
, *A. Venanzi (cofirst author)
1
, *G.
Schiavoni (cofirst author)
1
, S. G. Milner
1
, R. Limongello
1
, A. Santi
1
, V.
Pettirossi
1
, S. Ultimo
1
, L. Tasselli
1
, A. Pucciarini
1
, L. Falini
1
, S.
Sciabolacci
1
, M. P. Martelli
1
, P. Sportoletti
1
, S. Ascani
1
, ^B. Falini (co
last author)
1
, ^E. Tiacci (colast author)
1
1
Institute of Hematology and Center for HematoOncology Research,
University and Hospital of Perugia Italy, Medicine, Perugia, Italy
Introduction: Clonal hematopoiesis (CH) is frequent in the elderly
and predisposes to hematological malignancies, mostly of myeloid
and Tcell origin. CH incidence and tissue trajectories are not well
characterized in classical Hodgkin lymphoma (cHL), a Bcell neoplasm
frequent in the young and uniquely featuring a small tumor clone of
FIGURE 1
SUPPLEMENT ABSTRACTS
-
289
Hodgkin/ReedSternberg (HRS) cells interspersed in a tumor
supportive microenvironment largely infiltrated by hematopoietic
cells.
Methods: 40 cHL cases were studied for CH, by wholeexome and/or
targeted sequencing (mean unique coverage 150X and 1000X,
respectively) of microdissected tumor cells, and matched non
neoplastic blood cells (n = 27 cases) and/or lymphoid cells micro-
dissected from the tissue biopsy (n = 14 cases).
Results: 5/40 cases (12.5%) had blood and/or tissue CH, including 3/5
with >70 years and 2/35 < 70 years (Fig. 1A). In 3/5 CH cases (aged
30, 45 and 73 years), CH extensively spread through the non
neoplastic tissue microenvironment (32%, 92%, and 60% of cells),
being respectively driven by DNMT3A
R882H
(Case 1), mutant
KRAS
G60D
(Case 2) and DNMT3A
R882H
+ TET2
Q1274*
(Case 5).
Notably, in Case 5 (73 years old), CH originated also the tumor cell
clone, which was infected by the EpsteinBarr virus and had almost
no other somatic mutations exomewide; this is the first description,
in a cHL tumor cell clone, of mutant DNMT3A
R882
, a hotspot in
myeloid and Tcell neoplasms.
In Case 1 (45 years old), the same mutation determined a massive
blood CH (DNMT3A
R882H
in 94% leukocytes and in 96% B cells) that
was surprisingly absent from the tumor cell clone (instead carrying
STAT6 and SOCS1 mutations, typical of cHL) and led, 6 years after
therapy for cHL, to a likely therapyunrelated NPM1mutated acute
myeloid leukemia (with normal karyotype, wildtype TP53 and
PPM1D) (Fig. 1B). Thus, CH trajectories must be carefully disen-
tangled to correctly interpret the histogenesis and pathogenesis of
multiple blood cancers arising in patients with CH.
Interestingly, all 3 cases with extensive CH propagation in cHL tissue
microenvironment, showed a polyclonal status of Tcell receptor
gene rearrangement, thus proving that CHassociated mutations
occurred in a bone marrow stem/progenitor cell before Tcell lineage
commitment.
Finally, all these 3 cases progressed after firstline chemotherapy,
versus 11/35 (31%; pvalue 0.043) evaluable cases with absent or
nonextensive tissue CH, who otherwise had similar clinical features
and received the same firstline therapy.
Conclusions: CH can be observed in the cHL tissue, can originate the
tumor clone and can propagate to large part of its microenvironment.
Considering that both HRS cells and the microenvironment sup-
porting its growth play key roles in cHL pathogenesis, CH might
contribute to the development of this Bcell lymphoma and influence
its prognosis.
EA previously submitted to AACR and EHA 2021.
The research was funded by: This research was funded by a grant on
cHL to ET from AIRC (IG 2019 ID. 23732 project P.I. Tiacci Enrico); a
grant on AML to BF from AIRC (IG 2019 n. 23604); a grant on AML to
BF from ERC (Advanced Grant 2016 n. 740230), the Leopold Griffuel
prize from ARC to BF; and a grant on cHL to GS from the Department of
Medicine University of Perugia (Ricerca di Base 20172019).
Keywords: Tumor Biology and Heterogeneity, Hodgkin lymphoma
No conflicts of interest pertinent to the abstract.
PEDIATRIC LYMPHOMAS
208 | A UK POPULATIONBASED STUDY OF NONHODGKIN
LYMPHOMA IN TEENAGERS AND YOUNG ADULTS (TYA)
DELAYED DIAGNOSIS AND DEATH
R. Carr
1
, K. Stevens
2
, G. Anyaegbu
3
, J. Fidalgo
1
1
Guy's & St Thomas' Hospital, Haematology, London, UK,
2
University
Hospital Southampton, Haematology, Southampton, UK,
3
Addenbrookes
Hospital, Haematology, Cambridge, UK
Introduction: NonHodgkin Lymphoma may present with non
specific symptoms or lymphadenopathy, most commonly due to
infection. Late diagnosis of cancers in TYA patients is well recognised
and surveys of TYAs with cancer find many have repeated visits to
primary care physicians (GPs) before diagnosis. As part of a national
study of NHL in young adults information was recorded on the
pathway to diagnosis to understand the frequency and consequence
of diagnosis delay.
Methods: During 20152018 29 hospitals recruited newly diagnosed
patients aged 15–29y into an observational study of NHL diagnosis,
stage, treatment and survival. Information was requested on date of
first consultation with a medical professional, route to hospital
admission, ie. GP referral or self presentation to an emergency
department, and descriptions of repeated visits. Delay was recorded
if there was >62 days between first consultation and diagnosis, a
clear history of relevant symptoms or signs before seeking medical
advice, or evidence of missed opportunities by GP or hospital to di-
agnose a malignancy. In addition, the study received English Cancer
Registry data on 624 1529y old diagnosed over 3y 20152017,
recording diagnosis and deaths.
Results: Nine study hospitals contributed to this substudy; 171/191
patients had their diagnostic pathway recorded. Sixty (35%) had ev-
idence of delayed diagnosis recorded; by age group 1519y 21/45
(47%), 2024y 23/70 (33%), age 2429y 16/56 (29%). The most
frequent cause was patient delay in seeking advice (47%), delayed
referral by GP (28%), or hospital failure (25%), eg. diagnosing a pelvic
mass as ovarian cyst in 2 patients. Delay was not influenced by
gender: 34 male, 36 female. Advanced disease (stage 4) was more
common in delay patients 34/60 (57%), compared to 47% of similar
patients in the full cohort. Deaths, 10/60 (17%) in ‘delayed’ patients
compared to 16% in all recruited patients.
Cancer Registry data highlights the consequence of missed diagnosis.
Diagnosis and death date was the same for 6 individuals aged 20
29y; 2 confirmed as died at home, 1 immediately following hospital
admission, 3 without additional information. Another (23y) with T
lymphoblastic NHL died of cardiac tamponade 3 days after visting
an emergency department, but discharged.
Conclusions: The qualitative evidence from this substudy demon-
strates frequent failure to recognise malignancy in this age group, but
equally reluctance of patients to seek early medical advice for un-
usual symptoms and signs. The observation that mortality was similar
in frequency in the ‘delay’ subgroup compared to all patients on the
290
-
SUPPLEMENT ABSTRACTS
one hand suggests delayed diagnosis may not compromise outcome,
but equally may indicate that delay in seeking medical advice is to
some extent common to all. Achieving better outcomes needs raised
awareness by both young people and health professionals, as well as
expert treatment.
The research was funded by: Gilead UK and Ireland Fellowship
ProgrammeLeukaemia UK
Keywords: NonHodgkin (Pediatric, Adolescent, and Young Adult)
No conflicts of interest pertinent to the abstract.
PERIPHERAL T/NK CELL LYMPHOMAS
209 | A PHASE 2B OPENLABEL SINGLE ARM STUDY TO
EVALUATE THE EFFICACY AND SAFETY OF HBI8000
(TUCIDINOSTAT) IN PATIENTS WITH RELAPSED OR
REFRACTORY PERIPHERAL TCELL LYMPHOMA (PTCL)
W. S. Kim
1
, S. Rai
2
, K. Ando
3
, I. Choi
4
, K. Izutsu
5
, N. Tsukamoto
6
,
M. Yokoyama
7
, K. Tsukasaki
8
, J. Kuroda
9
, J. Ando
10
, M. Hidaka
11
,
Y. Koh
12
, H. Shibayama
13
, T. Uchida
14
, D. H. Yang
15
, K. Ishitsuka
16
,
K. Ishizawa
17
, J. S. Kim
18
, H. G. Lee
19
, H. Minami
20
, H. S. Eom
21
,
H. Nagai
22
, M. Kurosawa
23
, J. H. Lee
24
, W. S. Lee
25
, T. Shindo
26
,
D. H. Yoon
27
, S. Yoshida
28
, M. Gillings
29
, H. Onogi
30
, K. Tobinai
5
1
Samsung Medical Center, Division of HematologyOncology, Seoul, Ko-
rea,
2
Kindai University Hospital, Department of Hematology and Rheu-
matology, Faculty of Medicine, Osakasayama, Japan,
3
Tokai University
Hospital, Department of Hematology and Oncology, Isehara, Japan,
4
National Hospital Organization Kyushu Cancer Center, Department of
Hematology, Fukuoka, Japan,
5
National Cancer Center Hospital, Depart-
ment of Hematology, Tokyo, Japan,
6
Gunma University Hospital,
Oncology Center, Maebashi, Japan,
7
The Cancer Institute Hospital of
Japanese Foundation for Cancer Research, Department of Hematology
and Oncology, Tokyo, Japan,
8
International Medical Center, Saitama
Medical University, Department of Hematology, Saitama, Japan,
9
Kyoto
Prefectural University of Medicine, Division of Hematology and Oncology,
Kyoto, Japan,
10
Juntendo University Hospital, Department of Hematology,
Tokyo, Japan,
11
National Hospital Organization Kumamoto Medical
Center, Department of Hematology, Kumamoto, Japan,
12
Seoul National
University Hospital, Department of Internal Medicine, Seoul, Korea,
13
Osaka University Hospital, Department of Hematology and Oncology,
Suita, Japan,
14
Japanese Red Cross Nagoya Daini Hospital, Department of
Hematology and Oncology, Nagoya, Japan,
15
Chonnam National Univer-
sity Hwasun Hospital, Department of Hematology, Hwasun, Korea,
16
Kagoshima University Hospital, Department of Hematology and Rheu-
matology, Kagoshima, Japan,
17
Yamagata University Hospital, Depart-
ment of Third Internal Medicine, Yamagata, Japan,
18
Yonsei University
College of Medicine, Severance Hospital, Division of Hematology,
Department of Internal Medicine, Seoul, Korea,
19
Konkuk University
Medical Center, Department of Hematology & Oncology, Seoul, Korea,
20
Kobe University Graduate School of Medicine and Hospital, Department
of Medical Oncology/Hematology, Kobe, Japan,
21
National Cancer Center,
Center for Hematologic Malignancy, Goyangsi, Korea,
22
National Hos-
pital Organization Nagoya Medical Center, Clinical Research Center,
Nagoya, Japan,
23
National Hospital Organization Hokkaido Cancer Cen-
ter, Department of Hematology, Sapporo, Japan,
24
Gachon University Gil
Medical Center, Division of Hematology, Incheon, Korea,
25
Inje University
Busan Paik Hospital, Department of Internal Medicine, Busan, Korea,
26
Kyoto University Hospital , Department of Hematology and Oncology,
Kyoto, Japan,
27
Asan Medical Center, University of Ulsan College of
Medicine , Department of Oncology, Seoul, Korea,
28
National Hospital
Organization Nagasaki Medical Center, Department of Hematology,
Omura, Japan,
29
HUYA Bioscience International LLC, CEO & Executive
Chair, CA, USA,
30
HUYA Bioscience International, Executive Vice Presi-
dent, Head of Clinical DevelopmentJapan, Tokyo, Japan
Introduction: PTCL is a type of nonHodgkin lymphoma (NHL) and it
represents approximately 1020% of all NHL. Patients with relapsed
or refractory (R/R) PTCL have a poor prognosis. Although several
new agents for R/R PTCL have been developed, response rates are
generally modest and durations of response are relatively short.
Thus, there are still unmet needs for patients with R/R PTCL. HBI
8000 (tucidinostat) is a histone deacetylase inhibitor (HDACi) that
has been approved for treatment of PTCL in China.
Method: Patients after receiving 1 prior systemic therapy with a
histologically diagnosed as PTCL and at least 1 measurable lesion
received HBI8000 40 mg orally twice a week.
The primary endpoint was objective response rate (ORR) that was
evaluated by Independent Overall Efficacy Review Committee ac-
cording to the revised criteria for response assessment in lymphoma
(Cheson et al, 2014). Other endpoints included progressionfree
survival (PFS), duration of response (DOR) and safety. ORR was
also evaluated by subtypes.
The target ORR was 30% and the target number of patients for ef-
ficacy analysis was 40. AE severity was defined according to Common
Terminology Criteria for Adverse Events (CTCAE) Version 4.03. Our
study started in March 2017. We present the results of primary
analysis at the data cutoff date of 18 March 2019, when the last
patient completed the Cycle 5 Day 1. (NCT02953652)
Results: A total of 55 patients (median age: 71 years, range 3887)
received at least 1 dose of HBI8000. Overall, 69% (38/55) had
received 2 or more prior therapies, including 15% (8/55) of subjects
had received 5 or more therapies, before entering the study. The
median time from last treatment to the start of the study drug was
97 days (range: 29, 3861). As of data cutoff, 8 patients (15%) were
still on treatment. Median duration of exposure was 80 days (ranging
10580).
Among 46 patients in per protocol set, ORR was 46% (21/46 [95% CI:
31, 61]). ORR by subtype was 35% (12/34) in PTCLNOS; 88% (7/8)
in AITL; 33% (1/3) in ALCL, ALK; and 100% (1/1) in EATL. Median
PFS was 5.6 months and median DOR was 11.5 months. Median OS
was 22.8 months.
All 55 patients experienced adverse events. The incidence of
Grade 3 AEs was 84% and most AEs were laboratory abnor-
malities include thrombocytopenia (51%), neutropenia (36%) and
SUPPLEMENT ABSTRACTS
-
291
lymphopenia (22%). Serious AEs related to study drug were re-
ported in 18% (10/55). AEs led to study drug interruption or dose
reduction in 73% (40/55) and led to the discontinuation of study
drug in 33% (18/55), respectively.
Conclusions: Our results showed that tucidinostat has an efficacy
with acceptable safety profile in patients with R/R PTCL regardless of
its histopathological subtypes. This suggests that tucidinostat is a
clinically meaningful treatment option for patients with R/R PTCL
where no standard treatment is established, and strong unmet
medical needs exist.
The research was funded by: HUYA Bioscience International
Keywords: Therapeutics and Clinical Trials in Lymphoma Other
Conflicts of interests pertinent to the abstract
W. S. Kim
Research funding: Roche, Sanofi, Pfizer, J&J, Celltrion, Kyowakirin,
Donga ST, Mundipharma
S. Rai
Honoraria: Chugai
K. Izutsu
Research funding: HUYA Bioscience International
M. Yokoyama
Consultant or advisory role: Chugai
Research funding: Kyowakirin
K. Tsukasaki
Consultant or advisory role: DaiichSankyo, Ono, HUYA Bioscience
International, Yakult Honsha
Honoraria: Celgene, Chugai, Bayer, Eisai, Kyowakirin, Mundipharma,
Takeda
Research funding: DaiichSankyo, HUYA Bioscience International,
Celgene, Chugai, Bayer, Eisai
M. Hidaka
Honoraria: Janssen
Research funding: Chugai
Y. Koh
Employment or leadership position: GenomeOpinion
Stock ownership: GenomeOpinion
H. Shibayama
Consultant or advisory role: Chugai, Ono, Abbvie, and AstraZeneca
Honoraria: Takeda, Novartis, Celgene, Janssen, Chugai, Kyowakirin,
Ono, Eisai, Nippon Shinyaku, Otsuka, DaiichSankyo, BMS, Pfizer,
Sanofi, and Fujimoto
Research funding: Janssen, Novartis, Chugai, Ono, Eisai, HUYA
Bioscience International, Abbvie, AstraZeneca, Sanofi, Astellas, Teijin,
Shionogi, Taiho, Celgene, Takeda, MSD, Sumitomo Dainippon, Nippon
Shinyaku, and DaiichSankyo
K. Ishizawa
Research funding: Novartis, AbbVie, Bayer, SymBio, Otsuka, Pfizer,
Takeda, KyowaKirin
Other remuneration: Takeda, Celgene, Ono, Novartis, Chugai, Eisai
H. Minami
Honoraria: Bayer, BMS, Celgene, Chugai, DaiichSankyo, Sumitomo
Dainippon, Eisai, Janssen, KyowaKirin, Merck Serono, MSD, Ono,
Otsuka, Pfizer, Sanofi, Takeda, Genomic Health, Abbvie, Taiho, Lilly,
Novartis
Research funding: Astellas, Bayer, Behringer, BMS, Chugai, Daiich
Sankyo, Sumitomo Dainippon, Eisai, KyowaKirin, Merck Serono,
MSD, Nippon Shinyaku, Ono, Sanofi, Takeda, CSL Behring, Nippon
Fig. The Best Percent Change from Baseline in Total Tumor Size of Target Lesion (PPS)
292
-
SUPPLEMENT ABSTRACTS
Kayaku, Shionogi, Taiho, Lilly, Mitsubishi Tanabe, AZ, Pfizer, Amgen,
Novartis
H. Nagai
Honoraria: Eisai, Chugai, Takeda, Celgene, Mundipharma
Research funding: AstraZeneca, Celgene, Mundipharma, Zenyaku
Kogyo, Takeda, Chugai, Bayer
S. Yoshida
Research funding: KyowaKirin
M. Gillings
Employment or leadership position: HUYA Bioscience International
Stock ownership: HUYA Bioscience International
H. Onogi
Employment or leadership position: HUYA Bioscience International
K. Tobinai
Consultant or advisory role: Celgene, Zenyaku Kogyo, HUYA
Bioscience International, DaiichSankyo, Takeda, Mundipharma, Ono
Honoraria: Zenyaku Kogyo, Eisai, Takeda, Mundipharma, HUYA
Bioscience International, KyowaKirin, Celgene, Chugai, Ono, Yakult
Honsha, DaiichSankyo, Solasia
210 | A PHASE 2B STUDY TO EVALUATE THE EFFICACY AND
SAFETY OF TUCIDINOSTAT (HBI8000) IN JAPANESE PATIENTS
WITH RELAPSED OR REFRACTORY ADULT TCELL LEUKEMIA
LYMPHOMA (ATL)
K. Izutsu
1
, A. Utsunomiya
2
, T. Jo
3
, S. Yoshida
4
, K. Ando
5
, I. Choi
6
,
Y. Imaizumi
7
, K. Kato
8
, M. Kurosawa
9
, S. Kusumoto
10
, T. Miyagi
11
, E.
Ohtsuka
12
, O. Sasaki
13
, H. Shibayama
14
, K. Shimoda
15
, Y.
Takamatsu
16
, K. Takano
17
, K. Tsukasaki
18
, S. Makita
1
, K. Yonekura
19
,
J. Taguchi
3
, M. Gillings
20
, H. Onogi
21
, K. Tobinai
1
1
National Cancer Center Hospital, Department of Hematology, Tokyo,
Japan,
2
Imamura General Hospital, Department of Hematology,
Kagoshima, Japan,
3
Japanese Red Cross Nagasaki Genbaku Hospital,
Department of Hematology, Nagasaki, Japan,
4
National Hospital
Organization Nagasaki Medical Center, Department of Hematology,
Omura, Japan,
5
Tokai University Hospital, Department of Hematology/
Oncology, Kanagawa, Japan,
6
National Hospital Organization Kyushu
Cancer Center, Department of Hematology, Fukuoka, Japan,
7
Nagasaki
University Hospital, Department of Hematology, Nagasaki, Japan,
8
Kyushu University Hospital, Department of Hematology, Oncology &
Cardiovascular medicine, Fukuoka, Japan,
9
National Hospital
Organization Hokkaido Cancer Center, Department of Hematology,
Sapporo, Japan,
10
Nagoya City University Hospital, Division of
Hematology and Oncology, Aichi, Japan,
11
Heartlife Hospital, Department
of Hematology, Okinawa, Japan,
12
Oita Prefectural Hospital, Department
of Hematology, Oita, Japan,
13
Miyagi Cancer Center, Division of
Hematology, Miyagi, Japan,
14
Osaka University Hospital, Department of
Hematology and Oncology, Osaka, Japan,
15
University of Miyazaki
Hospital, Department of Hematology, Miyazaki, Japan,
16
Fukuoka
University Hospital, Department of Medical Oncology, Hematology and
Infectious Diseases, Fukuoka, Japan,
17
Oita University, Department of
Medical Oncology and Hematology, Faculty of Medicine, Oita, Japan,
18
International Medical Center, Saitama Medical University, Department
of Hematology, Saitama, Japan,
19
Imamura General Hospital, Department
of Dermatology, Kagoshima, Japan,
20
HUYA Bioscience International LLC,
CEO & Executive Chair, San Diego, USA,
21
HUYA Bioscience International
LLC, Executive Vice President, Head of Clinical DevelopmentJapan,
Tokyo, Japan
Introduction: Tucidinostat (HBI8000) is a class I selective oral his-
tone deacetylase inhibitor with immunomodulatory effects including
enhanced cellmediated toxicity, with activation of enhanced tumor
specific cytotoxic Tlymphocytes and suppression of regulatory T
lymphocytes.
In the phase 1 study in Japanese patients with relapsed or re-
fractory (R/R) nonHodgkin lymphoma including those with adult
Tcell leukemialymphoma (ATL), tucidinostat showed tolerability
and manageable safety profile as well as efficacy signals especially
in patients with ATL. This phase 2 study further evaluated the ef-
ficacy and safety of tucidinostat in patients with R/R aggressive
ATL.
Method: Key inclusion criteria included; histopathological or cyto-
logical diagnosis of ATL of acute, lymphoma or unfavorable chronic
types; relapsed or refractory disease after receiving prior systemic
therapy including mogamulizumab or 1 prior systemic therapy with
cytotoxic chemotherapy in case of intolerance/contraindication for
mogamulizumab. Patients were to receive tucidinostat 40 mg twice a
week with a 28day cycle. Tucidinostat was continued until disease
progression or the development of unacceptable toxicity. The pri-
mary endpoint was objective response rate (ORR). Secondary end-
points included progressionfree survival (PFS), duration of response
(DOR) and safety. (NCT02955589)
Results: A total of 23 patients were treated with tucidinostat and
were included in both efficacy and safety analysis sets. The median
age was 72 years (range: 6089), and 35% (8/23) were female. The
median number of prior chemotherapies was 2. All patients had prior
mogamulizumab treatment. As for ATL subtype, acute, lymphoma and
unfavorable chronic types constitute 57% (13/23), 35% (8/23), and
9% (2/23), respectively. The median time from last treatment to the
initiation of the study drug was 89 days (range: 30496).
Out of 23 patients, 7 showed objective responses including 1
complete response, and ORR was 30% [95% CI: 13, 53]. ORR by ATL
subtypes were 46% (6/13) in acute type, 13% (1/8) in lymphoma type,
and 0% (0/2) in unfavorable chronic type. Median PFS and median
DOR were 1.7 months and 6.5 months, respectively.
All 23 patients experienced adverse events (AEs). Overall, 78%
(18/23) of patients had AEs of Grade 3 severity. Most of AEs were
hematologic including thrombocytopenia and neutropenia, followed
by nonhematological AEs including decreased appetite and malaise.
Conclusions: The results of the present study are demonstrating
efficacy in patients with R/R aggresive ATL with prior treatment
SUPPLEMENT ABSTRACTS
-
293
history of mogamulizumab. Toxicities were mainly hematologic,
which were manageable with supportive care and dose modifications.
This phase 2b study demonstrated that tucidinostat had clinically
meaningful efficacy and an acceptable safety profile in R/R aggressive
ATL.
The research was funded by: HUYA Bioscience International
Keywords: Aggressive Tcell nonHodgkin lymphoma, Therapeutics
and Clinical Trials in Lymphoma Other
Conflicts of interests pertinent to the abstract
K. Izutsu
Research funding: HUYA Bioscience International
A. Utsunomiya
Consultant or advisory role: HUYA Bioscience International, JIMRO
Honoraria: Novartis Pharma, Kyowa Kirin, Daiichi Sankyo, Bristol
Myers Squibb, Celgene, Pfizer, Minophagen Pharmaceutical, Jans-
sen Pharmaceutical, Chugai Pharmaceutical
S. Yoshida
Research funding: Kyowa Kirin
Y. Imaizumi
Honoraria: Celgene, Kyowa Kirin, Eisai , BristolMyers Squibb,
Sumitomo Dainippon Pharma, SymBio Pharmaceuticals
K. Kato
Consultant or advisory role: AbbVie, AstraZeneca, Celgene, Chugai
Pharmaceutical, Eisai, Janssen Pharmaceutical, Novartis Pharma,
Daiichi Sankyo, Ono Pharmaceutical
Honoraria: Takeda Pharmaceutical, MSD, Kyowa Kirin, Janssen
Pharmaceutical, Celgene, Ono Pharmaceutical, Mundipharma, Sumi-
tomo Dainippon Pharma, BristolMyers Squibb
Research funding: Chugai Pharmaceutical, Takeda Pharmaceutical,
Kyowa Kirin, AbbVie, Eisai, Janssen Pharmaceutical, Celgene, Ono
Pharmaceutical, Novartis Pharma, Daiichi Sankyo
S. Kusumoto
Honoraria: Chugai Pharmaceutical
H. Shibayama
Consultant or advisory role: Chugai Pharmaceutical, Ono Pharma-
ceutical, AbbVie, AstraZeneca
Honoraria: Takeda, Novartis, Celgene, Janssen, Chugai, Kyowa Kirin,
Ono, Eisai, Nippon Shinyaku, Otsuka, Daiichi Sankyo, BristolMyers
Squibb, Pfizer, Sanofi, Fujimoto
Research funding: Janssen, Novartis, Chugai, Ono, Eisai, HUYA
Bioscience International, AbbVie, AstraZeneca, Sanofi, Astellas, Tei-
jin, Shionogi, Taiho, Celgene, Takeda, MSD, Sumitomo Dainippon
Pharma, Nippon Shinyaku, Daiichi Sankyo
K. Shimoda
Consultant or advisory role: Novartis Pharma, Takeda Pharmaceu-
tical, BristolMyers Squibb, Celgene
Research funding: Perseus Proteomics, Pharma Essentia Japan,
AbbVie, Astellas Pharma, MSD, Chugai Pharmaceutical, Kyowa Kirin,
Pfizer, Novartis Pharma, Otsuka Pharmaceutical, Asahi Kasei Medical
Y. Takamatsu
Research funding: Takeda Pharmaceutical, Ono Pharmaceutical,
Chugai Pharmaceutical, Kyowa Kirin, Taiho Pharmaceutical
K. Tsukasaki
Consultant or advisory role: Daiichi Sankyo, Ono Pharmaceutical,
HUYA Bioscience International, Yakult Pharmaceutical Industry
Honoraria: Celgene, Chugai Pharmaceutical, Bayer Yakuhin, Eisai,
Kyowa Kirin, Mundipharma, Takeda Pharmaceutical
Research funding: Daiichi Sankyo, HUYA Bioscience International,
Celgene, Chugai Pharmaceutical, Bayer Yakuhin, Eisai
S. Makita
Honoraria: Celgene/BMS, Daiichi Sankyo, Eisai, Novartis Pharma,
Takeda Pharmaceutical
K. Yonekura
Honoraria: AbbVie, Celgene, Daiichi Sankyo, Eisai, Eli Lilly Japan,
Janssen Pharmaceuticals, Kaken Pharmaceutical, Kyowa Kirin, Mar-
uho, Minophagen Pharmaceutical, Novartis Pharma, Sanofi, Taiho
Pharmaceutical, Torii Pharmaceutical, UCB Japan
M. Gillings
Employment or leadership position: HUYA Bioscience International
Stock ownership: HUYA Bioscience International
H. Onogi
Employment or leadership position: HUYA Bioscience International
K. Tobinai
Consultant or advisory role: Celgene, Zenyaku Kogyo, HUYA
Bioscience International, Daiichi Sankyo, Takeda Pharmaceutical,
Mundipharma, Ono Pharmaceutical
Honoraria: Zenyaku Kogyo, Eisai, Takeda Pharmaceutical, Mundi-
pharma, HUYA Bioscience International, Kyowa Kirin, Celgene,
Chugai Pharmaceutical, Ono Pharmaceutical, Yakult Pharmaceutical
Industry, Daiichi Sankyo, Solasia Pharma
211 | A PHASE II TRIAL OF REDUCED DOSE BRENTUXIMAB
VEDOTIN FOR CUTANEOUS TCELL LYMPHOMAS
N. Khan
1
, S. Noor
2
, S. Geller
3
, M. S. Khodadoust
4
, M. Kheterpal
5
,
H. Hancock
1
, T. Davey
1
, S. Ryu
1
, L. Perez
1
, A. Lares
4
, N. Ganesan
1
,
S. Sohail
1
, A. Santarosa
1
, N. Galasso
1
, E. Kim
4
, P. Myskowski
2
,
Y. H. Kim
4
, S. Horwitz
1
, A. Moskowitz
1
1
Memorial Sloan Kettering Cancer Center, Medicine, Lymphoma Service,
New York, USA,
2
Memorial Sloan Kettering Cancer Center, Dermatology,
New York, New York, USA,
3
Tel Aviv Sourasky Medical Center,
Dermatology, Tel Aviv, Israel,
4
Stanford University School of Medicine,
Department of Medicine, Division of Oncology & Department of
294
-
SUPPLEMENT ABSTRACTS
Dermatology, Stanford, California, USA,
5
Duke University Medical Center,
Dermatology, Durham, North Carolina, USA
Introduction: Mycosis fungoides (MF) is the most common cutaneous
T cell lymphoma. Brentuximab vedotin (BV) is a highly effective
therapy for MF with an overall response rate (ORR) of 65% in the
phase III ALCANZA trial (Prince et al, Lancet 2017). However, 44/66
(67%) of patients on BV developed peripheral neuropathy (PN) (G2, n
= 21; G3, n = 6), limiting treatment duration (median, 12 cycles). We
hypothesized that lower dose BV would produce acceptable efficacy
with reduced PN for the treatment of MF.
Methods: This is a multicenter phase II study. We treated BVnaïve
patients with MF (n = 19) in a Simon twostage design with ex-
pected ORR 35% and desired ORR of 65%. Patients were treated
with BV at 0.9 mg/kg. If <11 responses were seen at the end of
the second stage, the Simon 2 stage design restarted with BV at
1.2 mg/kg.
Responses are graded every 4 cycles. Global response is graded
using the International Society for Cutaneous Lymphomas consensus
criteria (Olsen et al, JCO 2011). PN is graded using Common Ter-
minology Criteria for Adverse Events v. 4.0 (CTCAE) and the Total
Neuropathy Score Clinical (TNSc). Health Related Quality of Life
(HRQoL) is selfreported by patients using the FACTLym, FACT
GOGNTX and Skindex29 questionnaires.
Results: 19 patients were treated in Cohort 1 with BV at 0.9 mg/kg,
with ORR of 42% (8 partial responses (PR), 0 complete responses
(CR)) (Fig 1A). Median PFS was 21.9 months (95% CI, 4.8 NR) and
median duration of response was 21.1 mon (95% CI, 5.9NR). Median
time to best response was 2.5 months (range, 2.1 7.8 mon), or 3
cycles (range, 311 cycles) (Fig 1A). 8/19 (42%; 95% CI, 2066%)
patients developed PN. 5/8 (63%) developed grade 1 (G1) PN at a
median of 5 cycles (range, 3.5 11); 3/8 (37%) patients developed G2
PN at a median of 18 cycles (range, 1319). Median time of PN re-
covery from G2 to G1 is 1.6 mon; median recovery from PN G1 to
resolution is 6.1 mon. Additional BVrelated adverse events seen in
>10% of patients included increased ALT (G1, n = 4), increased AST
(G1, n = 3; G2, n = 1), diarrhea (G1, n = 3), fatigue (G1, n = 2; G2, n =
1); infusionrelated reaction (G1, n = 3; G2, n = 1), localized edema
(G1, n = 2), maculopapular rash (G1, n = 1; G2, n = 1; G3, n = 1), pain
in extremity (G2, n = 2), pruritus (G1, n = 2; G3, n = 1) and nausea
(G1, n = 2).
Conclusion: Treatment with BV at 0.9 mg/kg resulted in an ORR of
42% (95% CI, 2066%) which did not meet the primary efficacy
endpoint. However, we observed a lower rate of G2 PN than re-
ported with full dose therapy in ALCANZA. We are now enrolling BV
naïve patients in Cohort 1 for treatment with BV at 1.2 mg/kg. We
are also enrolling patients in an exploratory cohort of patients pre-
viously treated with BV, and a second exploratory cohort of patients
with LyP. We continue to collect correlative data on HRQoL, PN and
the tumor microenvironment.
The research was funded by: Seattle Genetics
Keywords: Cutaneous nonHodgkin lymphoma
Conflicts of interests pertinent to the abstract
FIGURE 1 Swimmer's plot. 1A indicates response of MF patients in Cohort 1
SUPPLEMENT ABSTRACTS
-
295
N. Khan
Research funding: Seattle Genetics
S. Noor
Consultant or advisory role: Kyowa Kirin
S. Horwitz
Consultant or advisory role: Acrotech Biopharma, ADC Therapeutics,
Astex, C4 Therapeutics, Celgene, Janssen, Kura Oncology, Kyowa
Hakko Kirin, Myeloid Therapeutics, ONO Pharmaceuticals, Seattle
Genetics, Shoreline Bio, Takeda, Trillium Therapeutics, Tubulis,
Verastem, SecuraBio, and Vividion Therapeutics.
Research funding: ADC Therapeutics, Affimed, Aileron, Celgene, Daii-
chi Sankyo, Forty Seven, Inc., Kyowa Hakko Kirin, Millennium /Takeda,
Seattle Genetics, Trillium Therapeutics, and Verastem/SecuraBio.
A. Moskowitz
Honoraria: Imbrium Therapeutics L.P, Janpix Ltd., Merck, Seattle
Genetics, and Takeda
Research funding: ADC Therapeutics, Miragen, Seattle Genetics,
Merck, BristolMyers Squibb, and Incyte
212 | POPULATIONBASED COHORT STUDY OF THE EFFICACY
OF BRENTUXIMABVEDOTIN IN RELAPSED SYSTEMIC
ANAPLASTIC LARGE CELL LYMPHOMA USING PUBLIC HEALTH
ENGLAND DATA
S. Halligan
1
, M. J. Grainge
2
, N. MartinezCalle
3
, C. P. Fox
3
,
M. Bishton
3
1
Nottingham University Hospitals NHS Trust, School of Medicine,
Nottingham, UK,
2
University of Nottingham, Division of Epidemiology and
Public Health, School of Medicine, Nottingham, UK,
3
Nottingham
University Hospitals NHS Trust, Department of Haematology,
Nottingham, UK
Introduction: Systemic anaplastic large cell lymphoma (sALCL) is a T
cell lymphoma, historically associated with low cure rates following
relapse. Following a pivotal phase II study (Pro et al), the immuno
conjugate Brentuximab Vedotin (BV) became available in England
via the Cancer Drugs Fund (CDF) in 2013. To date, no largescale
populationbased studies have described outcomes following BV.
Public Health England (PHE) collects information on all cancer di-
agnoses in England, and since April 2012 all delivered Systemic Anti
Cancer Therapy (SACT). We aimed to evaluate whether routinely
collected PHE data can reliably assess outcomes of patients with
lymphoma.
Methods: We requested anonymised Office of Data Release (ODR)
information on sALCL patients 18 years treated with BV mono-
therapy between 1
st
Jan 201431
st
Dec 2019. We excluded primary
cutaneous and breastimplant associated ALCL, patients in the
ECHELON2 trial and BV received in combination. We requested
baseline demographics, ALK protein status, dates of BV cycles, SACT
data prior to and following BV, and prior autologous/allogeneic stem
cell transplantation (SCT). KaplanMeier survival methods were used
to compare the primary outcome of allcause mortality between
groups defined by age, gender and ALK status in univariate analyses.
Results: 173 patients were identified, of whom 46 were excluded. The
final cohort comprised 127 patients with r/r ALCL with a median age of
60 years at initiation of BV and median follow up time of 10 months. 49
(38.6%) patients were ALK + ve and 78 (61.4%) ALKve. 106 (83.5%)
received BV second line, and 13 (10.2%) third or fourth line. 95 (74.8%)
received CHOP first line. Based on SACT data 18 (14.2%) received SCT
in first remission (16 auto, 2 allo). The median number of BV cycles
received was five. Median 2year overall survival (OS) was 46.6%. The
majority (59) of deaths occurred within the first 18 months, followed by
a survival plateau with only four subsequent deaths. There was no
difference in OS between ALK+ve and ALKve (p = 0.78), age <40 vs
40 years(p = 0.89), age <60 vs 60(p = 0.96), between genders(p =
0.25), or receiving prior SCT (p = 0.55). Two patients received SCT after
BV, with both alive 18+ months posttransplant. Receiving BV as
second line therapy was associated with improved survival, with 2year
OS of 50.3% versus 29.7% for those third or fourth line (p = 0.03).
Conclusions: We confirm BV is a highly effective treatment for r/r
sALCL with real world survival outcomes across subgroups highly
comparable with clinical trial data. Study weaknesses include lack of
information on toxicity and data from double blind studies, although
this data is now being collected. Analysis of routinely collected PHE
data offers the opportunity to undertake high quality, nationwide
populationbased studies, to inform the efficacy of highcost drugs
such as BV in routine clinical practice.
Keywords: Aggressive Tcell nonHodgkin lymphoma,
Immunotherapy
No conflicts of interest pertinent to the abstract.
213 | PHASE 1 RESULTS OF ANTIPDLIGAND 1
(DURVALUMAB) & LENALIDOMIDE IN PATIENTS WITH
CUTANEOUS T CELL LYMPHOMA AND CORRELATION WITH
GENE EXPRESSION PROFILE
C. S. Querfeld
1
, N.C. Tsai
2
, J. Palmer
3
, X. Martinez
4
, F. Abdulla
5
, X.
Wu
6
, S. T. Rosen
7
, J. Zain
8
1
City of Hope, Beckman Research Institute and Dept. of Pathology,
Duarte, California, USA,
2
City of Hope, Division of Biostatistics, Duarte,
296
-
SUPPLEMENT ABSTRACTS
California, USA,
3
City of Hope, Division of Biostatistics, Duarte, California,
USA,
4
City of Hope, Division of Dermatology, Duarte, California, USA,
5
City of Hope, Division of Dermatology, Duarte, California, USA,
6
City of
Hope, Integrative Genomics Core, Duarte, California, USA,
7
City of Hope,
Hematology and Hematopoietic Cell Transplantation, Duarte, California,
USA,
8
City of Hope, Hematology and Hematopoietic Cell Transplantation,
Duarte, California, USA
Background: T cells in CTCL are functionally exhausted, charac-
terized by the expression of immune inhibitory molecules (Cancer
Immunol Res 6; 2018). These findings justify the evaluation of
immune checkpoint inhibition to reverse T cell exhaustion in CTCL.
We initiated a phase 1/2 clinical trial of lenalidomide and durva-
lumab (NCT03011814) to determine the safety and efficacy of this
regimen. Durvalumab is a human monoclonal antibody with high
affinity and selectivity for PDL1, targeting exhausted T cells and
distinct cells within their environment. Lenalidomide, an oral
immunomodulatory drug (IMiD) has previously shown activity in
CTCL (Blood 123; 2014). Durvalumab may restore an antitumor
immune response, and the combination of durvalumab/lenalido-
mide may enhance immune checkpoint blockadeinduced immune
responses.
Methods: Pts were enrolled in sequential cohorts to receive durva-
lumab (fixed dose at 1500 mg) and dose escalation of lenalidomide
(dose level 1 = 10 mg for all cycles; dose level 2 = 10 mg for cycle 1,
15 mg for all subsequent cycles; dose level 3 = 10 mg for cycle 1, 15
mg for cycle 2, and 20 mg for all subsequent cycles) to characterize
safety, efficacy and antitumor activity. Serial skin samples were
collected to assess the impact on tumor cells and tumor
microenvironment.
Results: 10 males/3 females, median age 36 (29–72 y), with aggres-
sive or refractory/advanced CTCL, clinical stages IB (2), IIA (3), IIB (6),
IIIA (1), and aggressive epidermotropic CD8 + CTCL (1) and a median
of prior systemic treatments of 3 (range, 28) were enrolled. Dose
level 1 (n = 3), dose level 2 (n = 3), dose level 3 (n = 4). Median follow
up time was 16.1 months (range, 3.736.1) months. No serious AEs or
DLTs were observed during the DLT evaluation period (cycles 13).
The most frequently reported AEs were fatigue (n = 8), skin pain (n =
4), chills (n = 3), anemia (n = 3), and leukopenia (4). One grade 3
maculopapular rash (possibly due to lenalidomide) was observed, all
other treatmentrelated AEs were grade 1/2 in severity. One pt
discontinued treatment due to fatigue. Three pts developed grade 1/
2 autoimmune thyroiditis that resolved with treatment. Median cy-
cles of treatment were 7 (range, 128). Median duration of response
was 6 (range, 1 28+) months. Nine pts achieved PR, 2 pts maintained
stable disease and 2 pts developed PD. Three pts remain on treat-
ment. Gene expression levels for several checkpoints were analyzed.
Conclusions: AntiPDL1/lenalidomide has significant clinical activity
in refractory/advanced CTCL, which will be formally evaluated in the
Phase 2 portion. Responses were durable and ongoing, and treatment
was well tolerated. Dose escalation is up to maximum dose of 20 mg
lenalidomide daily. Our preliminary results reveal adaptive and
innate immune signatures that may be predictive of response to
checkpoint blockade and yield insights into mechanisms of thera-
peutic resistance.
The research was funded by: This research was funded in part
through an NIH/NCI Cancer Center Support Grant (P30CA033572)
to City of Hope, NIH/NCI grant (R01 CA22951001) to C. Querfeld
and Leukemia Lymphoma Society Clinical Scholar Award to C.
Querfeld
Keywords: Immunotherapy, Targeting the Tumor Microenvironment
Conflicts of interests pertinent to the abstract
C. S. Querfeld
Consultant or advisory role: Helsinn, Kyowa Kirin, Bioniz, Miragen,
Trillium
Research funding: Celgene
214 | ROMIDEPSIN AND CARFILZOMIB IN RELAPSED /
REFRACTORY PERIPHERAL TCELL LYMPHOMA WITH
ASSESSMENT OF H23B AS A PREDICTIVE BIOMARKER THE UK
NCRI SEAMLESS PHASE 1/2 ROMICAR TRIAL
G. P. Collins
1
, S. Booth
2
, L. R. Cherrill
3
, D. Slade
3
, C. Morland
3
,
L. Hopkins
3
, E. Nagy
3
, K. Linton
4
, C. P. Fox
5
, D. Lewis
6
, A. Davies
7
,
G. Turner
8
, G. Rees
8
, C. Yap
9
, K. Cwynarski
10
1
NIHR Oxford Biomedical Research Centre, Churchill Hospital,
Haematology, Oxford, UK,
2
Churchill Hospital, Clinical Haematology,
Oxford, UK,
3
Birmingham University, Cancer Research UK Clinical Trials
Unit, Birmingham, UK,
4
Christie Hospital, Medical onology, Manchester,
UK,
5
Nottingham University Hospitals NHS Foundation Trust,
Haematology, Nottingham, UK,
6
Plymouth Hospitals NHS Trust,
Haematology, Plymouth, UK,
7
University of Southampton, CRUK/NIHR
Experimental Cancer Medicines Centre, Southampton, UK,
8
Oxford
University Hospitals NHS Foundation Trust, Cellular Pathology, Oxford,
UK,
9
Institute of Cancer Research, Clinical Studies, London, UK,
10
University College London Hospitals NHS Foundation Trust,
Haematology, London, UK
Introduction: Relapsed/refractory Peripheral Tcell lymphoma
(PTCL) has poor outcomes. The histone deacetylase inhibitor
(HDACi) romidepsin (ROMI) has a reported overall response rate
(ORR) of 25%, median progression free survival (PFS) of 4 months
and some longterm responses. Carfilzomib (CAR) is a proteasome
inhibitor synergising with HDACis in a number of cancer cell lines.
HR23B expression is hypothesised to be a predictive biomarker of
HDACi response based on in vitro data suggesting it is required for
cancer cell lethality. The RomiCar trial aimed to determine the
maximum tolerated dose (MTD) of the combination of ROMI and
CAR and the best ORR over the first 8 cycles with assessment of
HR23B as a predictive biomarker.
Methods: Phase (Ph) 1 used the continual reassessment method
(CRM) to determine the MTD of ROMI with CAR defined as the dose
closest to 25% probability of occurrence of a dose limiting toxicity
SUPPLEMENT ABSTRACTS
-
297
(DLT) during cycle 1. Six dose levels were planned. The CRM design
allowed more rapid accrual: once the maximum 3 patients were on
the dose level under evaluation, further patients received the dose
level below, with all data contributing to dose decisions. Ph 2 used a
single stage A’Hern design to assess best ORR during the first 8
cycles (assessed using the Revised Response Criteria for Malignant
Lymphoma) of the combination in all participants (pts) treated at the
MTD. ROMI was given IV on days 1, 8 and 15 of a 28d cycle; CAR IV
on days 1, 2, 8, 9, 15 and 16. HR23B expression was performed on
formalin fixed paraffin embedded tissue.
Results: 33 pts enrolled to Ph 1 with 27 evaluable for MTD assess-
ment. 34 pts were treated at the MTD and evaluable for Ph 2. Me-
dian age 62y (2282y); 69% male; median prior treatment lines 2
performance status 0 (44%), 1 (44%) or 2 (10%) (1 unknown); 53%
refractory to last treatment. 51% had PTCL Not Otherwise Specified;
40% angioimmunoblastic Tcell lymphoma. 7 DLTs were seen in 6
patients during phase 1. The MTD was defined as ROMI 10 mg/m
2
with CAR 20mg/m
2
for 2 doses then 40mg/m
2
, giving an estimated
posterior DLT probability of 0.216 with a 90% credible interval
(0.106, 0.352). The ORR at the MTD was 32% (95% confidence in-
terval 1949%): 15% complete response, 18% partial response, 18%
stable disease. Grade 3/4 adverse events in 10% pts were anaemia
(17%); neutropenia (35%); thrombocytopenia (42%). Median PFS was
4.0 months (median follow up 19 months); 4 participants remain on
treatment. HR23B expression was not associated with response with
27% (3 of 11) HR23B positive pts responding.
Conclusion: The combination of ROMI and CAR is safe and tolerable
in R/R PTCL with MTD declared efficiently by a flexible CRM trial
design. Treatment at the MTD gave an ORR of 32% and median PFS
of 4.0 months which was similar to the ROMI phase 2 trial. HR23B
expression did not appear to be associated with response and R/R
PTCL remains a significant area of unmet need.
The research was funded by: Blood Cancer UK, BMS and Amgen
Keywords: Aggressive Tcell nonHodgkin lymphoma
Conflicts of interests pertinent to the abstract
G. P. Collins
Consultant or advisory role: Celgene, a Bristol Myers Squibb
company
Honoraria: Celgene, a Bristol Myers Squibb company
Research funding: Celgene, a Bristol Myers Squibb company and
Amgen
K. Linton
Consultant or advisory role: Celgene, a Bristol Myers Squibb
Company
Honoraria: Celgene, a Bristol Myers Squibb Company
C. P. Fox
Consultant or advisory role: Celgene, a Bristol Myers Squibb
company
Honoraria: Celgene, a Bristol Myers Squibb company
Educational grants: Celgene, a Bristol Myers Squibb company
A. Davies
Consultant or advisory role: Celgene, a Bristol Myers Squibb
company
Honoraria: Celgene, a Bristol Myers Squibb company
Research funding: Celgene, a Bristol Myers Squibb company
Educational grants: Celgene, a Bristol Myers Squibb company
K. Cwynarski
Consultant or advisory role: Celgene, a Bristol Myers Squibb
company
Honoraria: Celgene, a Bristol Myers Squibb company
Educational grants: Celgene, a Bristol Myers Squibb company
215 | SINTILIMAB PLUS CHIDAMIDE FOR RELAPSED/
REFRACTORY (R/R) EXTRANODAL NK/T CELL LYMPHOMA
(ENKTL): A PROSPECTIVE, MULTICENTER, SINGLEARM, PHASE
IB/II TRIAL (SCENT)
H. Huang
1
, Y. Gao
1
, X. Wang
1
, B. Bai
1
, L. Zhang
2
, Y. Xiao
2
, X. Liu
2
,
W. Li
3
, Q. Cai
1
, Z. Li
1
, Y. Chen
4
, W. Xu
5
, R. Feng
6
, H. Wu
7
, J. Li
8
,
X. Wu
9
1
Sun Yatsen University Cancer Center, Department of Medical Oncology,
Guangzhou, China,
2
Union Hospital affiliated to Tongji Medical College of
Huazhong University of Science and Technology, Cancer Center,
Wuhan, China,
3
Guangdong General Hospital, Guangdong Academy of
Medical Sciences, Department of lymphoma, Guangzhou, China,
4
Guangdong General Hospital, Guangdong Academy of Medical Sciences,
Department of pathology, Guangzhou, China,
5
the First Affiliated Hospital
of Nanjing Medical University, Jiangsu Province Hospital, Department of
Hematology, Nanjing, China,
6
Nanfang Hospital, Southern Medical
298
-
SUPPLEMENT ABSTRACTS
University, Department of Hematology, Guangzhou, China,
7
Hubei Cancer
Hospital affiliated to Huazhong University of Science and Technology,
Department of lymphoma, Wuhan, China,
8
Sun Yatsen University Cancer
Center, Department of Clinical Research, Guangzhou, China,
9
Geneseeq
Technology Inc., Translational Medicine Research Institute, Toronto,
Canada
Background: Patients with r/r ENKTL have a poor prognosis after
failing asparaginase based regimen, and there is lack of effective
treatment. ORIENT4 trial demonstrated Sintilimab (a fully human
antiPD1 antibody) was effective and well tolerated in r/r ENKTL(J
Clin Oncol 37, 2019 (suppl; abstr 7504)). Chidamide, an oral
subtypeselective histone deacetylase inhibitor (HDACi) showed
efficacy for r/r ENKTL. Moreover, accumulating evidences have
shown the synergism between histone deacetylase inhibitor and
antiPD1 antibody. This trial was designated to evaluate the effi-
cacy and safety of the novel combination of Sintilimab plus Chida-
mide in r/rENKTL.
Methods: This study enrolled patients with histologically confirmed
r/rENKTL failed from asparaginasebased regimen. In Phase Ib, a
standard “3+3” design was utilized to identify the MTD, DLT and
recommended Phase II dosage (RP2D) of Chidamide plus Sintili-
mab. In phase II, patients received Sintilimab (200mg) plus Chi-
damide (RP2D) every 21 days for up to 1 year or until PD,
intolerable toxicity, withdrawal of consent. The primary endpoint
was ORR assessed by investigators per RECIL 2017 criteria (NCT
03820596).
Results: From March 2019 to January 2021, 38 eligible patients
were enrolled in China. Of 37 response evaluable patients, 22
patients (59.5%) achieved an ORR including 18 (48.6%) patients
with CR (Figure 1). With median followup time of 12.7 months
(range, 0.9 to 21.5), the median TTR was 6.0 weeks (range, 5.0
to12.4) and median DOR was 13.3+ months (range, 1.3 to 19.2+,
Figure 2). Estimated 18 months OS and PFS rate were 76.2% ±
6.9%, and 52.5% ± 8.7%, respectively. OS and PFS for patients
with CR/PR were superior to SD/PD (P < 0.001, Figure 3). We
assessed PDL1 (22C3) expression by combined positivity score
(CPS). The median CPS was 40.0, patients with CPS 30 exhibited
FIGURE 2 Treatment exposure and
response duration(n=38)
FIGURE 1 Best change in the SPD of target lesions from
baseline for all patients in the evaluable set(n=37)
SUPPLEMENT ABSTRACTS
-
299
benefit more from the combination than their counterparts with
CPS < 30. Both ctDNA and EBVDNA clearance had promising
predictive value for survival. Twentyfive (65.8%) patients reported
TRAEs. The most frequently observed (10%) TRAEs were
neutropenia (65.8%), thrombocytopenia (44.4%), anemia (44.4%),
hypothyroidism (47.4%), hypoproteinemia (36.8%), transaminase
increased (26.3%), nausea and vomiting (26.2%). The most frequent
Grade (G) 3 TRAEs were neutropenia (28.9%), thrombocytopenia
(10.5%). Immunerelated AEs were reported in 18 (47.4%) pa-
tients including a G4 exfoliative dermatitis and an interstitial
pneumonia. TEAEs that led to permanent treatment discontinua-
tion occurred in two (5.3%) patients. No death was related to the
study drug.
Conclusion: Sintilimab combined with Chidamide showed manage-
able safety profile and yielded effective antitumor activity, durable
response in patients with r/r ENKTL for the first time. It is a prom-
ising therapeutic option for this population, especially for those with
CPS 30. The combination of PD1 antibody and HDACi may rep-
resents a novel strategy for r/r ENKTL. Further investigation is
warranted.
The research was funded by: Innovent Biologics Inc.
Keywords: Immunotherapy, Aggressive Tcell nonHodgkin lym-
phoma, Extranodal nonHodgkin lymphoma
No conflicts of interest pertinent to the abstract.
216 | A PHASE I
B
STUDY OF AN ORAL PI3Kδ INHIBITOR
LINPERLISIB IN PATIENTS WITH RELAPSED OR REFRACTORY
PERIPHERAL T CELL LYMPHOMA
L. Qiu
1
, J. Jin
2
, H. Cen
3
, K. Zhou
4
, X. Xu
5
, F. Li
6
, T. Wu
7
, H. Yang
8
, Z.
Wang
9
, Z. Li
10
, H. Bao
11
, Z. Xu
12
, Y. Shu
13
1
Blood Institute of the Chinese Academy of Medical Sciences,
lymphoma treatment center, Tianjin, China,
2
First Hospital Affiliated
Zhe Jiang Medical University, Department of Hematology, Hangzhou,
China,
3
Guangxi Medical University Affiliated Tumor Hospital,
Department of Medical Oncology, Nanning, China,
4
Henan Cancer
Hospital, Department of Hematology, Zhengzhou, China,
5
Cancer
Hospital affiliated to Nantong University, Department of Hematology
and Lymphoma, Nantong, China,
6
The First Affiliated Hospital of
Nanchang University, Department of Hematology, Nanchang, China,
7
Guizhou Cancer Hospital, Department of Lymphoma, Guiyang, China,
8
Cancer Hospital of The University of Chinese Academy of Sciences,
Department of Lymphoma, Hangzhou, China,
9
Linyi Cancer Hospital,
Department of Medical Oncology, Linyi, China,
10
Sun YatSen Univer-
sity Cancer Center, Department of Medical Oncology, Guangzhou,
China,
11
Shanghai Yingli Pharmaceutical Co., Ltd, Clinical Management
Department, Shanghai, China,
12
Shanghai Yingli Pharmaceutical Co.,
Ltd, Clinical Management Department, Shanghai, China,
13
Shanghai
Yingli Pharmaceutical Co., Ltd, Clinical Management Department,
Shanghai, China
FIGURE 3 OS and PFS. (A)OS of whole cohort. (B)PFS of whole cohort. (C)OS of CR/PR vs SD/PD. (D)PFS of CR/PR vs SD/PD
300
-
SUPPLEMENT ABSTRACTS
Background: Linperlisib is an oral highly selective small molecule
inhibitor of PI3Kδ that is welltolerated with a favorable PK profile in
patients with lymphomas and advanced solid tumors. This phase I
b
study is evaluating the efficacy and safety of Linperlisib in relapsed or
refractory peripheral Tcell lymphoma (PTCL), a highly aggressive
malignancy with few treatment options for patients.
Methods: Eligible PTCL patients that had received at least 1 prior
systemic therapy were administered Linperlisib 80mg orally once
daily (RP2D) in 28 day cycles until disease progression, unacceptable
toxicity, or withdrawal from the study. Tumor response was assessed
by IWG 2007 criteria with CT performed every 2 cycles. The primary
endpoint was the overall response rate (ORR), and the secondary
endpoint was toxicity assessed by NCICTCAE5.0.
Results: As of March 5
th
, 2021, 38 PTCL patients were enrolled in
this exploratory trial. Most patients were stage III (39.5%) or IV
(52.6%). Of the 30 evaluable patients, the PTCL histologies were
PTCLNOS (n = 13), AITL (n = 11), ALCL (n = 3), NKTCL (n = 2) and
MEITL (n = 1). With the 30 evaluable patients, 21 had Investigator
confirmed responses for a 70% ORR, including 33.3% CR (10 pt) and
36.7% PR (11 pt). In two of the major subtypes, ORR was 46.2% (6/
13) PTCLNOS and 81.8% (9/11) AITL, respectively. Most responses
occurred by first assessment at C2D28. A disease control rate of
100% was observed, and 24 patients (80% of evaluable patients) are
still receiving linperlisib treatment, with 8 patients >6 cycles of
followup to date. 36 patients experienced at least 1 TRAE in the
trial, with 94.6% of AEs grade 2. There were no unexpected tox-
icities, consistent with other lymphoma patients who had been
treated with linperlisib previously. The most common TRAEs (10%
all grades) were neutrophil count decreased (57.9%), leukocyte count
decreased (36.8%), hypertriglyceridemia (21.1%), aspartate amino-
transferase increased (15.8%), hypercholesterolemia (15.8%), alanine
aminotransferase increased (15.8%), creatinine increased (10.5%),
rash (10.5%), platelet count decreased (10.5%) and electrocardio-
gram T wave abnormal (10.5%). No AE grade 4 was observed, and
AEs grade 3 were neutrophil count decreased (10.5%), leukocyte
count decreased (2.6%), stomatitis (2.6%), platelet count decreased
(2.6%), pneumonia (2.6%) and blood lipase increased (2.6%). 7 pa-
tients (18.4%) experienced at least one SAE, in which 5 (13.2%) SAEs
were considered to be drugrelated, including neutrophil count and
leukocyte count decreased (1), gastritis (1), and pneumonia (3).
Conclusion: Linperlisib showed significant activity in r/r PTCL pa-
tients and was well tolerated with manageable toxicities. With these
promising findings, further study of the treatment of PTCL by Lin-
perlisib is warranted. Clinical Trial Information: NCT04108325.
Sponsor: Shanghai Yingli Pharmaceutical.
EA previously submitted to ASCO 2021.
The research was funded by: Shanghai Yingli Pharmaceutical Co., Ltd
Keywords: Molecular Targeted Therapies
Conflicts of interests pertinent to the abstract
H. Bao
Employment or leadership position: Chief medical officer
Z. Xu
Employment or leadership position: general manager
Y. Shu
Employment or leadership position: Associate Chief Medical Officer
217 | IMPACT OF RITUXIMAB ON TREATMENT OUTCOMES OF
PATIENTS WITH ANGIOIMMUNOBLASTIC TCELL LYMPHOMA;
A POPULATIONBASED ANALYSIS
F. O. Meeuwes
1
, M. Brink
2
, M. W.M. van der Poel
3
, M. J. Kersten
4
,
Mariël. Wondergem
4
, P. G.N.J. Mutsaers
5
, L. H. Böhmer
6
,
S. WoeiAJin
7
, O. Visser
8
, R. Oostvogels
9
, P. M. Janssen
10
,
G. A. Huls
11
, J. S.P. Vermaat
12
, M. Nijland
11
1
Martini Hospital, Department of Hematology, Groningen, Netherlands,
2
Netherlands Comprehensive Cancer Organisation (IKNL), Department of
Research and Development, Utrecht, Netherlands,
3
Maastricht University
Medical Center, Department of Hematology, Maastricht, Netherlands,
4
Amsterdam University Medical Centers, Department of Hematology,
Amsterdam, Netherlands,
5
Erasmus MC, Department of Hematology,
Rotterdam, Netherlands,
6
Haga Ziekenhuis, Department of Hematology,
The Hague, Netherlands,
7
UZ Leuven, Department of Hematology, Leuven,
Belgium,
8
Isala Hospital, Department of Hematology, Zwolle, Netherlands,
9
University Medical Center Utrecht, Department of Hematology, Utrecht,
Netherlands,
10
Leiden University Medical Center, Department of
Pathology, Leiden, Netherlands,
11
University Medical Center Groningen,
Department of Hematology, Groningen, Netherlands,
12
Leiden University
Medical Center, Department of Hematology, Leiden, Netherlands
Introduction: Angioimmunoblastic Tcell lymphoma (AITL) is a
mature Tcell malignancy that is often accompanied by paraneo-
plastic phenomena due to immune deregulation. Patients are treated
with cyclophosphamide, doxorubicin, vincristine, and prednisone with
or without etoposide (CHO(E)P) followed by high dose chemotherapy
in younger patients. In the majority of patients, EBVpositive, CD20
positive Bcells are present in the tumor infiltrate. It has been
postulated that targeting these Bcells with the antiCD20 mono-
clonal antibody rituximab might improve outcome, but this has only
been studied in small series. This nationwide, populationbased study
evaluated the impact of rituximab on best response and overall
survival (OS) of patients with AITL treated with CHO(E)P.
Methods: All patients with AITL diagnosed between 20142018 and
treated with at least one cycle of CHO(E)P with or without rituximab
were identified in the Netherlands Cancer Registry (NCR), with
survival followup through February 1, 2021. Baseline characteristics,
best response and survival outcomes were collected. OS was defined
as the time from AITL diagnosis to allcausedeath. Multivariable
analysis of OS was performed using Cox regression.
Results: Overall, 237 patients with AITL received CHO(E)P (median
age, 66 years; 62% male; 97% stage IIIV). Rituximab was added to
CHO(E)P in 100 patients (42%). Similar mean age and Ann Arbor
stage were found in patients treated with CHO(E)P and RCHO(E)P.
SUPPLEMENT ABSTRACTS
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301
There was a predominance of female patients in the CHO(E)P group
as compared to the RCHO(E)P group (45% vs. 30%, P = 0.023). For
both the CHO(E)P and the RCHO(E)P group, the proportion of pa-
tients who received etoposide (30% vs. 33%; P = 0.702) and
consolidation with an autologous stem cell transplantation (ASCT)
(29% for both) was comparable. The best overall response (complete
remission and partial remission) rate for patients who received CHO
(E)P and RCHO(E)P was 73% and 82%, respectively (P = 0.105;
Figure 1A). The median follow up was 52.3 months. The 5year OS
were 46% and 43% for patients who received CHO(E)P or RCHO(E)
P (P = 0.822, Figure1B), respectively. Age, sex, and addition of
etoposide and/or rituximab to CHOP were not associated with OS.
Consolidation with ASCT, however, significantly improved prognosis
(Hazard ratio 0.25, 95% confidence interval 0.140.43; P < 0.001).
Conclusion: In this large cohort of patients, the addition of rituximab
to CHO(E)P did not improve OS. To our knowledge, this study reports
the largest nationwide and populationbased cohort published on this
subject thus far.
Keywords: Aggressive Tcell nonHodgkin lymphoma
No conflicts of interest pertinent to the abstract.
218 | ROMIDEPSINCHOEP PLUS UPFRONT STEMCELL
TRANSPLANTATION IN PERIPHERAL TCELL LYMPHOMA (PTCL):
FIRST ANALYSIS OF THE PHASE II FILPTCL13 STUDY
A. Chiappella
1
, C. Carniti
2
, A. Re
3
, C. Castellino
4
, A. Evangelista
5
,
R. Ciancia
6
, L. Orsucci
7
, A. Pinto
8
, S. V. Usai
9
, A. Arcari
10
, F. Ilariucci
11
,
F. G. Rossi
12
, F. Benedetti
13
, L. Flenghi
14
, C. Ghiggi
15
, A. L. Molinari
16
,
V. Stefoni
17
, S. Volpetti
18
, V. R. Zilioli
19
, F. Ballerini
20
, R. Bruna
21
,
F. Cavallo
22
, G. Musuraca
23
, C. Patti
24
, F. Re
25
, M. Tani
26
,
M. Varettoni
27
, M. Zanni
28
, A. Dodero
1
, S. A. Pileri
29
, G. Ciccone
5
,
P. Corradini
30
1
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Hematology
and Stem Cell Transplantation, Milano, Italy,
2
Fondazione IRCCS, Istituto
Nazionale dei Tumori di Milano, Laboratory of Hematology, Division of
Hematology and Stem Cell Transplantation, Milano, Italy,
3
ASST Spedali
Civili di Brescia, Hematology Division, Brescia, Italy,
4
Azienda Ospedaliera
S. Croce e Carle, Division of Hematology, Cuneo, Italy,
5
Azienda
Ospedaliera e Universitaria Città della Salute e della Scienza and CPO
Piemonte, Unit of Clinical Epidemiology, Torino, Italy,
6
Centro di
Riferimento Oncologico (CRO) IRCCS, Oncohematology and Stem Cell
Transplantation and Cellular Therapies, Aviano, Italy,
7
Azienda Ospeda-
liera e Universitaria Città della Salute e della Scienza, Division of Hema-
tology, Torino, Italy,
8
Istituto Nazionale Tumori, Fondazione G. Pascale,
IRCCS, HematologyOncology & Stem Cell Transplantation Unit, Napoli,
Italy,
9
Ospedale Oncologico Armando Businco, Hematology, Cagliari, Italy,
10
Ospedale Guglielmo da Saliceto, Hematology Unit, Piacenza, Italy,
11
Azienda USLIRCCS, Hematology, Reggio Emilia, Italy,
12
Fondazione
IRCCS Granda, OM Policlinico, Division of Hematology, Milano, Italy,
13
Azienda Ospedaliera Universitaria di Verona, Hematology and Stem Cell
Transplantation, Verona, Italy,
14
Azienda Ospedaliera di Perugia, Hema-
tology, Perugia, Italy,
15
IRCCS Ospedale Policlinico San Martino, Hema-
tology, Genova, Italy,
16
Ospedale degli Infermi, Hematology, Rimini, Italy,
17
University of Bologna, Institute of Hematology “Seràgnoli”, Bologna,
Italy,
18
Presidio Ospedaliero Universitario “Santa Maria della Miser-
icordia” di Udine, ASUFC, Clinic of Hematology, Udine, Italy,
19
ASST
Grande Ospedale Metropolitano Niguarda, Division of Hematology,
Milano, Italy,
20
IRCCS Ospedale Policlinico San Martino, Clinic of He-
matology, Genova, Italy,
21
Ospedale Maggiore Della Carità, Division of
Hematology, Novara, Italy,
22
University of Torino; Azienda Ospedaliera e
Universitaria Città della Salute e della Scienza, Division of Hematology,
Department of Molecular Biotechnologies and Health Sciences, Torino,
Italy,
23
IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino
Amadori”, Division of Hematology, Meldola, Italy,
24
Azienda Villa Sofia
Cervello, Division of OncoHematology, Palermo, Italy,
25
Azienda
OspedalieraUniversitaria di Parma, Hematology and CTMO, Parma, Italy,
26
Ospedale Santa Maria delle Croci, Hematology Unit, Ravenna, Italy,
27
Fondazione IRCCS Policlinico San Matteo, Division of Hematology,
Pavia, Italy,
28
Azienda Ospedaliera Santi Antonio e Biagio e Cesare Arrigo,
Division of Hematology, Alessandria, Italy,
29
European Institute of
302
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SUPPLEMENT ABSTRACTS
Oncology IRCCS, Division of Haematopathology, Milano, Italy,
30
Chair of
Hematology, University of Milano; Fondazione IRCCS Istituto Nazionale
dei Tumori di Milano, Division of Hematology and Stem Cell Trans-
plantation, Milano, Italy
Introduction: Peripheral Tcell lymphomas (PTCL) are a rare disease
with a poor prognosis, even when treated with high dose chemo-
therapy and stem cell transplantation (HDC + SCT). Romidepsin (Ro),
a histone deacetylase inhibitor, showed activity in relapsed or re-
fractory PTCLs, with a good profile of safety.
Methods: In the phase Ib FILPTCL13 (NCT02223208), we tested
the combination of Ro with cyclophosphamide, doxorubicin, eto-
poside, vincristine, dexamethasone (CHOEP) plus HDC + SCT in
young PTCLs patients eligible to transplant, and we defined 14
mg/ms the maximum tolerated dose of Ro. Aim of the phase II
part of the study was to evaluate the efficacy (response rate,
progression free survival, PFS, at 18months and overall survival,
OS) of RoCHOEP followed by HDC + SCT. The primary objective
of the study was to demonstrate a 15% increase in 18months PFS
for the combination RoCHOEP plus HDC + SCT, compared to the
literature data (from 55% to 70%, planned sample size = 110).
Patients aged 1865 eligible to SCT, with advanced PTCLNOS,
angioimmunoblastic/Thelper follicular and ALK negative anaplastic
large cell lymphoma were eligible. Treatment plan consisted of 6
courses of RoCHOEP every 21 days (14 mg/ms Ro day 1 and 8),
followed by cisplatincytarabinedexamethasone (DHAP) with stem
cell harvest and SCT. Patients in complete response (CR) after
induction proceeded to autoSCT, while those in partial response
(PR), with an available HLAmatched donor, proceeded to alloSCT
upfront.
Results: From September 2017 to October 2020, 83 patients were
enrolled into the phase II part of the study; median age was 55
years (IQR 49;59); 74 (89%) had stage IIIIV and 29 (35%) IPI risk
>2. An interim analysis was performed, according to the statistical
plan, when the first 75 patients were enrolled. At a median
followup of 12 months, the estimated 18months PFS was 53%
(95% CI: 0.390.64) and the OS was 79% (95% CI: 0.660.87). On
74 patients evaluable for response after induction, the overall
response rate (ORR) after 6 RoCHOEP was 72% (53 patients),
with 59% (44 patients) complete response (CR). On 65 patients
evaluable for end of treatment response, the ORR after SCT was
42/65 (65%), with 36 (55%) CR. The most frequent toxicities
during RoCHOEP treatment were hematological, with grade 34
neutropenia and thrombocytopenia in 35% and 37% of cycles,
respectively.
Conclusions: The interim analysis demonstrated an 18months PFS
of 53%; based on these results, which demonstrated a PFS super-
imposable to those obtained with conventional HDC+SCT, the
enrollment was stopped. In conclusion, the addition of Romidepsin to
CHOEP did not ameliorate prognosis in newly diagnosis PTCLs
eligible to SCT.
The research was funded by: Romidepsin was provided free by
Celgene.
Keywords: Chemotherapy, Combination Therapies, Stem Cell
Transplant
No conflicts of interest pertinent to the abstract.
219 | FRONTLINE BRENTUXIMAB VEDOTIN AND CHP (A
+CHP) IN PATIENTS WITH PERIPHERAL TCELL LYMPHOMA
WITH LESS THAN 10% CD30 EXPRESSION (SGN35032, TRIAL IN
PROGRESS)
D. Jagadeesh
1
, S. Knowles
2
, S. M. Horwitz
3
1
Cleveland Clinic Taussig Cancer Institute and Case Comprehensive
Cancer Center, Hematology and Medical Oncology, Cleveland, Ohio, USA,
2
Seagen Inc., Late Stage Development, Bothell, Washington, USA,
3
Memorial Sloan Kettering Cancer Center, Lymphoma Service, New York,
New York, USA
Introduction: In the ECHELON2 phase 3 clinical trial, brentuximab
vedotin, a CD30directed antibodydrug conjugate, combined with
cyclophosphamide, doxorubicin, and prednisone (A+CHP) showed
efficacy in patients (pts) with peripheral Tcell lymphoma (PTCL)
across a range of CD30 expression levels, including the lowest
eligible level of 10% by IHC.
It is expected that A+CHP will demonstrate efficacy in PTCL
with <10% CD30 expression because: i) clinical responses to bren-
tuximab vedotin occurred in pts with low and undetectable CD30
expression (Jagadeesh 2019); and ii) the activity of CHP chemo-
therapy in PTCL is unrelated to CD30 expression. This study will
include subjects with PTCL subtypes other than systemic anaplastic
large cell lymphoma (sALCL).
Methods: This is a dualcohort, openlabel, multicenter, phase 2
clinical trial (EudraCT 202000233674) designed to evaluate the
efficacy and safety of A+CHP in subjects with nonsALCL PTCL and
CD30 expression <10% on tumor cells. Up to approximately 40
subjects will be enrolled in each of the CD30 negative (expression
<1%) and the CD30 positive (expression 1% to <10%) cohorts. Only
subjects with CD30 expression <10% per central confirmation will be
analyzed for the primary and secondary endpoints. Subjects will
receive 21day cycles of A+CHP for a target of 68 cycles.
The primary endpoint of this trial is objective response rate
(ORR) per blinded independent central review (BICR) using the
Revised Response Criteria for Malignant Lymphoma (Cheson 2007).
Key secondary endpoints include complete remission (CR) and
progressionfree survival (PFS) per BICR and overall survival.
Key inclusion criteria include adults with newly diagnosed PTCL,
excluding sALCL, per the WHO 2016 classification; CD30 expression
<10% by local assessment; and FDGavid disease by PET and
measurable disease of at least 1.5 cm by CT, as assessed by the site
radiologist.
Lymphoma response and progression will be assessed by BICR
per Cheson 2007 and modified Lugano criteria (Cheson 2014). A PET
scan is required at baseline, after Cycle 4, and after the completion of
SUPPLEMENT ABSTRACTS
-
303
study treatment. Followup restaging CT scans will be performed
over the next two years.
Efficacy and safety endpoints will be summarized with
descriptive statistics by cohort, for both the CD30 negative and
the CD30 positive cohorts. Timetoevent endpoints, such as PFS,
will be estimated using KaplanMeier methodology and Kaplan
Meier plots will be presented. Medians for timetoevent ana-
lyses (eg, median PFS),will be presented and twosided 95% con-
fidence intervals will be calculated using the loglog transformation
method.
The trial currently is open at sites in the US. Sites in Europe are
expected to open in early 2021.
EA previously submitted to ASCO and EHA 2021.
The research was funded by: Seagen Inc.
Keywords: Aggressive Tcell nonHodgkin lymphoma, Combination
Therapies, Ongoing Trials
Conflicts of interests pertinent to the abstract
D. Jagadeesh
Employment or leadership position: Cleveland Clinic Taussig Cancer
Institute and Case Comprehensive Cancer Center
Consultant or advisory role: Atara Biotherapeutics, Verastem, Kyowa
Kirin
Research funding: Seagen Inc., Regeneron, MEI Pharma, Debiopharm
Group, Trillium Therapeutics, AstraZeneca, ADC Therapeutics, Rhi-
zen Pharmaceuticals
S. Knowles
Employment or leadership position: Seagen Inc., University of
Washington
Research funding: Seagen Inc.
Educational grants: Seagen Inc.
S. M. Horwitz
Employment or leadership position: Memorial Sloan Kettering Can-
cer Center
Consultant or advisory role: Celgene, Millennium, Kyowa Kirin, Sea-
gen, ADC Therapeutics, Portola, Verastem, Takeda, Astex, Kura
Oncology, Acrotech Biopharma, C4 Therapeutics, Janssen Oncology,
Trillium, Vividion, Myeloid Therapeutics, Ono
Research funding: Celgene, Seagen, Takeda, Kyowa Kirin, Aileron
Therapeutics, ADC Therapeutics, Verastem, Forty Seven, Trillium,
Daiichi Sankyo, Affimed, Portola, Corvus
220 | PERIPHERAL TCELL LYMPHOMAS INVOLVING CENTRAL
NERVOUS SYSTEM: A REPORT FROM THE CZECH LYMPHOMA
STUDY GROUP REGISTRY
H. Mocikova
1
, R. Pytlik
2
, K. Benesova
3
, A. Janikova
4
, J. Duras
5
, A.
Sykorova
6
, K. Steinerova
7
, V. Prochazka
8
, V. Campr
9
, D. Belada
6
, J.
Dlouha
10
, M. Trneny
3
1
University Hospital Kralovske Vinohrady and Third Faculty of
Medicine, Charles University, Department of Haematology, Prague,
Czech Republic,
2
Institute of Haematology and Blood Transfusion, Cell
Therapy Department, Prague, Czech Republic,
3
Charles University,
General Hospital, First Department of Medicine, Department of
Hematology, Prague, Czech Republic,
4
University Hospital Brno,
Department of Hematology and Oncology, Brno, Czech Republic,
5
University Hospital and Faculty of Medicine, Department of
HematoOncology, Ostrava, Czech Republic,
6
University Hospital and
Faculty of Medicine, 4th Department of Internal Medicine– Hematol-
ogy, Hradec Kralove, Czech Republic,
7
University Hospital , Department
of Clinical Hematology, Pilsen, Czech Republic,
8
Faculty of Medicine
and Dentistry, Palacky University, Department of HaematoOncology,
Olomouc, Czech Republic,
9
University Hospital Motol, Institute of Pa-
thology and Molecular Medicine, Prague, Czech Republic,
10
Czech
Lymphoma Study Group Registry, Data Management Office, Prague,
Czech Republic
Introduction: We analyzed the incidence, risk factors of central
nervous system (CNS) relapse and outcome of CNS involvement in
patients with peripheral Tcell lymphomas (PTCL) prospectively
observed in the Czech Lymphoma Study Group Registry
(NCT03199066).
Methods: Out of 1040 patients with peripheral Tcell lymphomas
(PTCL) we identified 29 patients (2.79%) with central nervous
system (CNS) involvement: 13 patients (1.25%) had CNS disease at
initial diagnosis and 16 patients (1.54%) at relapse. Median age at
initial CNS diagnosis was 61 years and at CNS relapse 54.5 years.
Initial CNS disease concurrently with systemic lymphoma involve-
ment was documented in 11 of 13 patients and at relapse in 12 of
16 patients. The incidence of meningeal involvement was compa-
rable at initial diagnosis and in CNS relapsed patients (9 vs 11).
Most common histology with CNS disease was PTCL not otherwise
specified (10 cases at initial diagnosis and 8 cases at relapse). CNS
prophylaxis was not used in PTCL. High dose methotrexate based
treatment was administered in 44.8% of patients with CNS
disease.
Results: Median followup of all patients with PTCL was 71.3
months. Median progressionfree survival (PFS) of all patients
was 32.6 months, with initial CNS disease 4.8 months and at CNS
relapse 5 months. Risk factors for CNS relapse included: involve-
ment of more than one extranodal site (p = 0.008), soft tissue
involvement (p = 0.003), testicular involvement (p = 0.046) and
presence of B symptoms (p = 0.035). Median overall survival (OS)
of all PTCL patients was 46 months, with initial CNS disease 18.2
months, at CNS relapse 11.8 months and at relapse outside of
CNS 18,9 months. CNS involvement was not associated with a
significantly worse OS compared with relapsed/refractory patients
without CNS involvement (p = 0.072).
Conclusions: The incidence of CNS disease at initial diagnosis and at
relapse in PTCL is low and concurrent systemic involvement is found
in most of these patients. The prognosis is poor, however, the
304
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SUPPLEMENT ABSTRACTS
outcome is comparable with relapsed systemic disease. Optimal
treatment is not yet defined.
Keywords: Aggressive Tcell nonHodgkin lymphoma
No conflicts of interest pertinent to the abstract.
221 | CLINICAL CHARACTERISTICS AND OUTCOMES OF
ADULT LYMPHOMAASSOCIATED HEMOPHAGOCYTIC
LYMPHOHISTIOCYTOSIS (HLH)
C. Y. Lee
1
, B. Wills Sanin
1
, S. A. Vardhana
1
, A. J. Moskowitz
1
1
Memorial Sloan Kettering Cancer Center, Medicine, New York, USA
Introduction: Lymphoma is a major cause of secondary HLH, a
lifethreatening hyperinflammatory syndrome due to immune dys-
regulation. This study examines the clinical and biological charac-
teristics, management, and outcomes of patients with lymphoma and
HLH.
Methods: We retrospectively reviewed 44 adult patients with
combined diagnoses of lymphoma and HLH at Memorial Sloan
Kettering Cancer Center between June 2012 and September 2020.
Overall survival (OS) was measured from the date of HLH diag-
nosis to the date of death or last followup. We evaluated the
association of demographic, clinical, laboratory, and treatment
variables on survival using logrank tests and Cox proportional
hazards model.
Results: Of the 44 patients, 30 (68%) had T and NKcell lym-
phoma, 12 (27%) had Bcell lymphoma, and 2 (5%) had Hodgkin
lymphoma. All but one patient received HLH therapy including
corticosteroids (95%), etoposide (68%), and intravenous immuno-
globulin (18%), which was initiated within 1 day of diagnosis in
84% of cases. Twentyfive patients (57%) received lymphoma
directed therapy with etoposide (n = 17) or without etoposide
(n = 8). Five of the 15 patients who underwent targeted tumor
sequencing of 400 genes harbored a TP53 mutation and all were
refractory to frontline therapy, while 7 of 10 patients without
TP53 mutation demonstrated initial treatment response (p = 0.03).
The median OS (mOS) of the entire cohort was 1.4 months, with a
30day cumulative mortality incidence of 36.4%. Most deaths were
attributed to relapsed or refractory HLH (n = 25/36, 69%) and
lymphoma progression (n = 6/36, 17%). Patients with T/NKcell
lymphomaassociated HLH had a mOS of 1.4 months compared to
9.2 months in Bcell lymphomas (p = 0.09). Ten patients (23%)
were diagnosed with HLH within 60 days of their initial lymphoma
diagnosis and had an improved prognosis (mOS 12.8 vs 1.3
months, p < 0.01). Treatment with etoposide, either alone or as
part of a lymphomadirected regimen, was associated with signif-
icantly improved survival (HR 0.48, 95% CI 0.240.96) whereas
lymphomadirected therapy with or without etoposide was not (HR
0.66, 95% CI 0.341.29). Significant predictors of mortality
included age 60 years, nonwhite race, and concurrent infection
during the hospitalization.
Conclusions: In this large cohort from a single U.S. institution, there
was a wide range of lymphoma subtypes associated with HLH.
Despite increased disease recognition and prompt initiation of
standard HLH and lymphomadirected therapies, the prognosis re-
mains very poor. Patients treated with etoposide had improved
survival, highlighting the importance of controlling hyper-
inflammation during initial management. Notably, TP53 mutation was
associated with primary refractory HLH. Future studies will aim to
elucidate the pathophysiology of lymphomaassociated HLH in order
to inform novel therapeutic approaches.
EA previously submitted to ASCO 2021.
The research was funded by: Lymphoma Research Foundation Lym-
phoma Clinical Research Mentoring Program
Keywords: Other
No conflicts of interest pertinent to the abstract.
TABLE 1 Clinical characteristics
TABLE 2 Lymphoma subtypes
SUPPLEMENT ABSTRACTS
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305
222 | HEPATOSPLENIC T CELL LYMPHOMA: CLINICAL
CHARACTERISTICS AND SURVIVAL
F. Baidoun
1
, M. Alhaj Moustafa
2
, H. W. Tun
2
, B. T. Hill
3
, D. Jagadeesh
3
1
Cleveland Clinic Foundation, Hospital Medicine Department, Cleveland,
USA,
2
Mayo ClinicFlorida, Hematology Oncology Division, Jacksonville,
Florida, USA,
3
Cleveland Clinic Foundation, Department of Hematology
and Medical Oncology, Cleveland, Ohio, USA
Introduction: Hepatosplenic T cell lymphoma (HSTCL) is a rare type
of T cell lymphoma (TCL) that accounts for <1% of nonHodgkin
lymphomas. Outcomes in this disease is dismal due to lack of effec-
tive standard therapy. In this study, we aimed to evaluate patient and
disease factors impacting overall survival (OS).
Materials and Methods: The national cancer database (NCDB) was
queried for patients diagnosed with HSTCL between 2004 and 2017.
All patients age 18 years diagnosed with hepatosplenic lymphoma
(ICDO 3 histology code 9716 was used to define the diagnosis)
were included. We excluded patients with multiple primary
malignancies, no follow up or unknown vital status. KaplanMeier and
multivariate Cox regression analyses were used to estimate OS and
to identify prognostic factors for survival.
Results: Of the 294 HSTCL patients included in the analysis, 200
(68%) were males, 194 (66%) Caucasian and 80 (27%) African
American. The median age at diagnosis was 46 (range 1888) years
and median followup was 62.3 ± 7.2 (95% CI 48.376.4) months.
Median overall survival for the whole cohort was 11.8 ± 1.4 (95% CI
8.9414.58) months. After excluding 81 patients (unknown chemo-
therapy status (n = 6), chemotherapy start time unknown (n = 61),
and treated entirely outside of the reporting facility (n = 14)), the
time to treat (TTT) from diagnosis to chemotherapy start was 7
days in 47 patients, within 829 days in 97 patients and 30 days in
69 patients. Patients with longer TTT (30 days) had superior median
OS (24.9 months) compared to patients who received treatment
sooner (7.1 months for 829 days and 8.8 months for 7 day group )
(P < 0.001 for both).
In univariate analysis, female gender was prognostic for OS
(median OS 23 vs 10 months, P = 0.011), but the type of treatment
FIGURE 1 Overall survival
306
-
SUPPLEMENT ABSTRACTS
had no impact splenectomy vs no splenectomy (median OS 11.22 vs
7.05 months, P = 0.113), hematopoietic stem cell transplantation
(HSCT) vs no HSCT (median OS 14.40 vs 11.30 months, P = 0.662)
and chemotherapy vs no chemotherapy (median OS 11.39 vs 10.02
months, P = 0.323).
Also, there was no difference in OS observed between different
treatment modalities [chemo only (143 patients), splenectomy
only (21 patients), chemo with splenectomy (51 patients), chemo
with HSCT (12 patients), splenectomy with chemo and HSCT
(10 patients)]. Compared to no treatment, only splenectomy
with chemotherapy was prognostic for OS (18.6 vs 2.9 months,
P = 0.030).
On multivariate analysis, female gender (HR 0.664 95% CI
0.4620.954; P = 0.027) and splenectomy (HR 0.611 95% CI 0.418
0.892; P = 0.011) were associated with better OS, whereas
chemotherapy and HSCT had no impact (HR 1.010 95% CI 0.634
1.608; P = 0. 967 and HR 0.951 95% CI 0.5631.607; P = 0. 852,
respectively).
Conclusion: In this large realworld cohort based analysis of HSTCL,
female gender and treatment with splenectomy were associated with
better OS, while chemotherapy and HSCT failed to improve survival.
Keywords: Aggressive Tcell nonHodgkin lymphoma
No conflicts of interest pertinent to the abstract.
223 | SUBTYPES OF MATURE T AND NK CELL LYMPHOMAS
ACCORDING TO 2016 WHO CLASSIFICATION. PRELIMINARY
REPORT OF THE INTERNATIONAL PROSPECTIVE TCELL
PROJECT 2.0
M. Federico
1
, C. S. Chiattone
2
, H. M. Prince
3
, A. Pavlovsky
4
, M.
Manni
1
, M. Civallero
1
, T. Skrypets
1
, C. A. De Souza
5
, E. A. Hawkes
6
, L.
Fiad
7
, A. Lymboussakis
1
, C. Tomuleasa
8
, R. Nair
9
, J. Pereira
10
, P.
Pereyra
11
, C. Minoia
12
, I. Kryachok
13
, N. S. de Castro
14
, R. H.
Advani
15
, S. Luminari
16
1
University of Modena and Reggio Emilia, Surgical, Medical and Dental
Department of Morphological Sciences related to Transplant, Oncology
and Regenerative Medicine, Modena, Italy,
2
Santa Casa de Sao Paulo,
School of Medical Sciences, São Paulo, Brazil,
3
Epworth Healthcare,
East Melbourne, Richmond, Australia,
4
Fundaleu, Haematology, Buenos
Aires, Argentina,
5
Universidade de Campinas, (UNICAMP), Campinas,
Brazil,
6
Lymphoma and Related Diseases Registry, School of Public
Health and Preventive Medicine Monash University and Olivia Newton
John Cancer Research Institute, Austin Health, Melbourne, Australia,
7
Hospital Italiano La Plata, Department of Hematology and Oncology,
Buenos Aires, Argentina,
8
Ion Chiricuta Oncology Institute, Department
of Hematology, Cluj Napoca, Romania,
9
TATA Medical Center, Clinical
Haematology Oncology, Kolkata, India,
10
Universidade de São Paulo,
Hospital das Clínicas da Faculdade de Medicina, São Paulo, Brazil,
11
Hospital Nacional Dr. Prof. Alejandro Posadas, Hematology, Buenos
Aires, Argentina,
12
IRCCS Cancer Institute "Giovanni Paolo II",
Haematology Unit, Bari, Italy,
13
National Cancer Institute,
Oncohematology Department, Kiev, Ukraine,
14
Hospital de Cancer de
Barretos, Hematology, Barretos, São Paulo, Brazil,
15
Stanford Cancer
Center, Blood and Marrow Transplant Program, Stanford, California,
USA,
16
Azienda Unità Sanitaria Locale IRCCS, Arcispedale Santa Maria
Nuova IRCCS, Hematology Unit and, University of Modena and Reggio
Emilia, Surgical, Medical and Dental Department of Morphological
Sciences related to Transplant, Oncology and Regenerative Medicine,
Reggio Emilia, Italy
Introduction: Mature T and NKcell lymphomas represent a het-
erogeneous group of lymphoid disorders (29 subtypes according
to the 2016 WHO classification) arising from mature T cells of
postthymic origin with different morphological characteristics,
phenotypes, and clinical presentation. Following the success of the
T Cell Project (TCP), which allowed the analysis of more than
1,500 cases of peripheral TCell lymphomas (PTCLs) collected
prospectively in 18 Countries, in 2018 the TCP 2.0 was launched.
Here we report the global distribution of PTCLs, from the cases
registered so far based on the locally established histological
diagnosis.
Methods: The TCP2.0 (ClinicalTrials.gov Identifier: NCT03964480) is
a prospective, international, observational study which adapts to
changes made in the new WHO classification.
Results: Since the beginning of the study (October 2018), 648 patients
with newly diagnosed PTCL were registered by 75 active centers
across 14 countries. Of these data, 594 patients have been validated
by the centralized trial office. Overall, PTCLNOS, Anaplastic large cell
lymphoma (ALCL) ALKnegative, and Angioimmunoblastic Tcell lym-
phoma (AITL), represent the most frequent subtypes, representing
31.3%, 18,9% and 13,5% of cases, respectively.
As reported in Table 1, PTCLNOS represents the most frequent
subtype worldwide, whereas Adult Tcell leukemia/lymphoma was
more frequent in Brazil, AITL and ALCL ALKnegative in Australia/
India, and ALCL ALKpositive in North America and Europe. Extra-
nodal NK/Tcell lymphoma, nasal type was relatively frequent in
Brazil and quite rare in the other Latin America Countries. Finally,
many subtypes represent less than 5% of cases in all geographic
areas.
Conclusions: The TCP2.0 continues to recruit very well, despite the
difficulties linked to the COVID19 pandemic, and may represent a
useful resource for the prospective study of this group of rare
lymphomas.
The research was funded by: Associazione Angela Serra per la
Ricerca sul Cancro
Keywords: Aggressive Tcell nonHodgkin lymphoma, Pathology and
Classification of Lymphomas
Conflicts of interests pertinent to the abstract
E. A. Hawkes
Other remuneration: Takeda, Roche
SUPPLEMENT ABSTRACTS
-
307
224 | CIRCULATING TUMOR DNA BY HIGHTHROUGHPUT
SEQUENCING OF T CELL RECEPTOR MONITORED TREATMENT
RESPONSE AND PREDICTED TREATMENT FAILURE IN T CELL
LYMPHOMAS
W. Wang
1
, W. Zhang
1
, Y. Zhang
1
, Y. Gan
1
, L. Qian
1
, D. Zhou
1
1
peking union medical college hospital, hematology, Beijing,
China
Introduction: Nextgeneration sequencing (NGS)based circulating
tumor DNA (ctDNA) detection is a promising monitoring tool
for lymphoid malignancies. Studies for T cell lymphoma are limited.
Objective: To explored whether nextgeneration sequencing (NGS)
based circulating tumor DNA (ctDNA) detection is applicable to T cell
lymphoma and assessed its performance in clinical settings.
Methods: We first identified tumor clones, identified as any CDR3
sequences that accounted more than 5%, by TCR sequencing in
pathological specimens. Then use these sequences to capture circu-
lating tumor DNA in plamsa. Any nonzero result in the plasma was
considered positive molecular disease. Results of ctDNA were
compared with PET/CT or the clinical outcome.
Results: 30 tumor and 74 blood samples were analyzed in our study.
Malignant clone was identified in 23 of the 30 (76.7%) tumor samples
through highthroughput sequencing (HTS) combined with PCR. We
detected the same tumor clone in plasma in 18 out of the 23 (78.3%)
patients. Circulating tumor DNA fraction correlated with lactate
dehydrogenase (LDH) (r = 0.52, p = 0.017), high level of ctDNA
predicted treatment failure (p = 0.0003) and there was a trend pa-
tients with high ctDNA burden would have poorer PFS. Furthermore,
ctDNA changed in concordance with clinical outcome and was more
sensitive than PET/CT. Also, recurrence of ctDNA was an important
clue for relapse.
Conclusion: In conclusion, our study indicated that ctDNA moni-
toring was suitable for T cell lymphoma. High level of pretreat-
ment ctDNA was a poor prognosis factor and changes of ctDNA
correlated well with clinical courses and was sensitive to find early
relapse.
EA previously submitted to EBMT, AACR, ASCO and EHA 2021.
The research was funded by: National Natural Science Foundation of
China (NSFC) (No. 81970188) CAMS Innovation Fund for Medical
Sciences(CIFMS) 201612M1001 Innovation project major
collaborative innovation 2019I2M2009 Beijing Municipal Natural
Science Foundation (BNSF) (No.7202154)
Keywords: Liquid biopsy
No conflicts of interest pertinent to the abstract.
308
-
SUPPLEMENT ABSTRACTS
225 | IMPACT OF DUSP22 REARRANGEMENT ON THE
PROGNOSIS OF SYSTEMIC ALKNEGATIVE ANAPLASTIC LARGE
CELL LYMPHOMA: A LYSA AND TENOMIC STUDY
D. Sibon
1
, B. Bisig
2
, C. Bonnet
3
, E. Bachy
4
, D. Cavalieri
5
, V. Fataccioli
6
,
F. Drieux
7
, J. Bruneau
8
, F. Lemonnier
9
, C. Bossard
10
, K.
Bouabdallah
11
, M. Parrens
12
, G. Damaj
13
, O. Tournilhac
5
, J. P. Jais
14
,
P. Gaulard
6
, L. de Leval
2
1
Necker University Hospital, Hematology, Paris, France,
2
Lausanne
University Hospital, Pathology, Lausanne, Switzerland,
3
Liège University
Hospital, Clinical Hematology Unit, Liège, Belgium,
4
LyonSud University
Hospital, Hematology, PierreBénite, France,
5
ClermontFerrand University
SUPPLEMENT ABSTRACTS
-
309
Hospital, Hematology, ClermontFerrand, France,
6
Mondor University
Hospital, Pathology, Créteil, France,
7
Henri Becquerel Cancer Center, Pa-
thology, Rouen, France,
8
Necker University Hospital, Pathology, Paris,
France,
9
Mondor University Hospital, Hematology, Créteil, France,
10
Nantes
University Hospital, Pathology, Nantes, France,
11
HautLévêque University
Hospital, Hematology, Bordeaux, France,
12
HautLévêque University Hos-
pital, Pathology, Bordeaux, France,
13
Caen University Hospital, Hematolo-
gy, Caen, France,
14
Necker University Hospital, Statistics, Paris, France
Introduction: ALKnegative anaplastic large cell lymphoma (ALCL) is
a CD30+ Tcell neoplasm which can sometimes harbour a DUSP22
rearrangement (DUSP22R) on 6p25.3. In the first clinical report, the
5year OS of 22 patients with DUSP22R was 90% (Parrilla Castellar
et al, Blood 2014). However, in a later work from the British
Columbia Cancer Lymphoid Cancer database, the 5year OS of 12
patients with DUSP22R was 40% (Hapgood et al, BJH 2019). Thus,
the prognostic impact of DUSP22R is currently unclear.
Methods: Systemic ALKnegative ALCL cases were collected through
the LYSA pathology institute and Tenomic, a transnational research
consortium on Tcell lymphomas involving several centers in France,
Belgium and Switzerland. For the purpose of the present study,
two expert hematopathologists (L.d.L. and P.G.) reviewed cases coded
as ALKnegative ALCL or CD30+ PTCLNOS and extended the
phenotypic analysis to reclassify them according to the WHO clas-
sification. FISH studies for DUSP22 and TP63 rearrangements were
carried out and analysed centrally. Clinical features and outcomes are
described.
Results: Among the 100 retrieved ALKnegative ALCL cases, 45
harboured a DUSP22R. As shown in the Table below, bone
involvement was the only significant parameter, more frequent in
DUSP22R cases (p = 0.01). Median followup of living patients was
4.3 years. 5year PFS was 32% for the 100 patients, including 46%
and 21% for the DUSP22R and nonR patients, respectively (p <
0.01). 5year OS was 50% for the 100 patients, including 57% and
45% for the DUSP22R and nonR patients, respectively (p = 0.32).
Conclusion: In our cohort, the largest to date, DUSP22R had no
statistically significant impact on OS.
Keywords: Diagnostic and Prognostic Biomarkers Aggressive Tcell
nonHodgkin lymphoma
No conflicts of interest pertinent to the abstract.
226 | SUBCUTANEOUS PANNICULITISLIKE TCELL
LYMPHOMA: MOLECULAR AND MUTATIONAL
CHARACTERIZATION COMPARED WITH LUPUS PANNICULITIS
AND HISTOPATHOLOGIC OVERLAPPING CASES
S. Machan
1
, M. Rodriguez
2
, R. Manso
2
, J. Borregon
2
, C. Chamizo
2
, R.
AlonsoAlonso
2
, S. Pérez Buira
2
, J. L. RodríguezPeralto
3
, L. Cerroni
4
,
L. Cereceda
2
, R. Córdoba
5
, M. Án. Piris
2
, L. Requena
1
, S. María
RodríguezPinilla
2
1
Fundación Jiménez DíazUniversidad Autónoma de Madrid,
Dermatology, Madrid, Spain,
2
Fundación Jiménez Díaz, Pathology,
Madrid, Spain,
3
Hospital Universitario 12 de Octubre, Pathology, Madrid,
Spain,
4
Medical University of Graz, Dermatology, Graz, Austria,
5
Fundación Jiménez Díaz, Hematology, Madrid, Spain
Clinical features at
diagnosis
DUSP22
rearranged
cases
DUSP22non
rearranged
cases p
N 45 55
Era 20042019 20012019
Median age, y (range) 60 (4086) 62 (3985) NS
Male 35/45 38/55 NS
PS 2 14/44 21/54 NS
Stage
1 4/45 3/55 NS
2 8/45 11/55
3 4/45 16/55
4 29/45 25/55
Extranodal site (any)
Bone 14/45 5/54 0.01
Liver 9/45 7/54 NS
Spleen 8/45 6/54 NS
Bone marrow 6/45 7/54 NS
Lung 7/45 4/54 NS
Skin 7/45 4/54 NS
Soft tissue 2/45 9/54 NS
GI tract 3/45 4/54 NS
Pleural effusion/ascites 1/45 0/54 NS
Blood 0/45 1/54 NS
Extranodal site >1 14/45 14/55 NS
Elevated LDH 28/44 29/54 NS
B2microglobulin 3
mg/L
7/21 16/34 NS
IPI
01 14/44 12/54 NS
2 8/44 15/54
3 10/44 15/54
45 12/44 12/54
Primary therapy
CHOP/CHOPlike 44/45 51/55 NS
Other regimen 0/45 3/55
Palliative care 1/45 1/55
Consolidative AutoSCT 7/45 5/55 NS
Consolidative AutoSCT 3/45 3/55 NS
310
-
SUPPLEMENT ABSTRACTS
Subcutaneous panniculitislike Tcell lymphoma (SPTCL) is a rare
cytotoxic primary cutaneous lymphoma whose histopathologic dif-
ferential diagnosis with lupus erythematosus panniculitis (LEP) can
be challenging, and overlapping cases have been described. In this
study we investigate whether gene expression profiling using a
customized NanoString platform may identify markers that can be
used to improve our understanding of the disease and to make a
more precise differential diagnosis. Twentytwo cases of SPTCL, LEP
and overlapping cases were analyzed using a customized NanoString
platform that includes 208 genes related to Tcell differentiation,
stromal signatures, oncogenes and tumor suppressor genes. Unsu-
pervised analysis of the gene expression of the samples identified
three clusters of samples that differentiated SPTCL from LEP sam-
ples. Most overlapping cases (4/5) were clustered with LEP cases, and
only one case was grouped with the SPTCL cases. We identified 60
and 30 genes that were respectively upregulated and downregulated
in SPTCL compared with LEP. Differentially expressed genes were
observed when comparing overlapping with LEP cases. Gene set
enrichment analysis recognized gene sets defining each group. We
identified mutations in epigenetic modificatory genes ARID1A, EZH2,
TET2, DNMT3A, and NCOR1; the tumor suppressor gene TP53, and
PLCG1 gene in four out of the six SPTCL samples analyzed. Only
one case showed HAVCR2 mutation. In conclusion, SPTCL
and LEP have distinctive molecular profiles. The molecular back-
ground of overlapping cases more closely resembles LEP than it does
SPTCL.
The research was funded by: Instituto de Salud Carlos III, from the
Ministry of Science and Innovation of Spain, PI17/2172.
Keywords: Diagnostic and Prognostic Biomarkers, Cutaneous non
Hodgkin lymphoma
No conflicts of interest pertinent to the abstract.
227 | CHARACTERIZATION OF THE ONCOGENIC PHENOTYPE
IN EXTRANODAL NATURAL KILLER/TCELL LYMPHOMA, NASAL
TYPE THROUGH GENE EXPRESSION PROFILE. SPANISH
LYMPHOMA GROUP GELTAMO
E. GonzálezBarca
1
, L. Gato
2
, A. Esteve
3
, R. SanzPamplona
4
, L.
Tomás
2
, M. Rodriguez
2
, A. Martín GarcíaSancho
5
, R. Córdoba
6
, A.
Monter
7
, M. Bastos
8
, J. M. Bergua Burgues
9
, M. J. Sayas
10
, M. C.
Viguria Alegria
11
, J. J. Sánchez Blanco
12
, M. Roig
13
, H. D. Luzardo
Henriquez
14
, R. Oña
15
, E. Cabezudo
16
, M. S. Infante
17
, J. A. Quei-
zan
18
, O. Blanco Nuñez
19
, A. Mozos
20
, F. Climent
21
, M. A. Piris
22
1
Institut Català d’Oncologia, Hospital Duran i Reynals, Institut
d’Investigació Biomèdica de Bellvitge (IDIBELL), Universitat de
Barcelona, Hematology, L’Hospitalet de Llobregat, Barcelona, Spain,
2
Fundación Jiménez Díaz, CIBERONC, Pathology, Madrid, Spain,
3
Insititut Català d'Oncologia, Unit of Biomarkers and Susceptibility,
Oncology Data Analytics Program (ODAP); Medical Oncology
Department, BARGO Badalona, Badalona, Barcelona, Spain,
4
Catalan
Institute of Oncology (ICO), Oncobell Program, Bellvitge Biomedical
Research Institute (IDIBELL) and CIBERESP, Unit of Biomarkers and
Susceptibility, Oncology Data Analytics Program (ODAP), L'Hospitalet
de Llobregat, Barcelona, Spain,
5
Hospital Universitario de Salamanca,
IBSAL, Hematology, Salamanca, Spain,
6
Fundación Jimenez Díaz, He-
matology, Madrid, Spain,
7
Hospital de la Santa Creu i Sant Pau, He-
matology, Barcelona, Spain,
8
Gregorio Marañón General University
Hospital (HGUGM), Hematology, Madrid, Spain,
9
Hospital San Pedro de
Alcántara, Hematology, Cáceres, Spain,
10
Hospital Universitario Dr
Peset, Hematology, Valencia, Spain,
11
Complejo Hospitalario de Nav-
arra, Hematology, Pamplona, Spain,
12
Hospital Morales Messeguer,
Hematology, Murcia, Spain,
13
Hospital La Fe, Hematology, Valencia,
Spain,
14
Hospital Dr Negrín, Hematology, Las Palmas de Gran Canaria,
Spain,
15
MD Anderson Cancer Center, Hematology, Madrid, Spain,
16
Insititut Català d'Oncologia, Hospital Moises Broggi, Hematology, San
Juan Despí, Barcelona, Spain,
17
Hospital Infanta Leonor, Hematology,
Madrid, Spain,
18
Hospital General de Segovia, Hematology, Segovia,
Spain,
19
Hospital Universitario de Salamanca, IBSAL, Pathology, Sala-
manca, Spain,
20
Hospital de la Santa Creu i Sant Pau, Pathology,
Barcelona, Spain,
21
Hospital Universitario de Bellvitge, Institut
d'Investigaciò Biomédica de Bellvitge IDIBELL, Pathology, Hospitalet de
LLobregat, Barcelona, Spain,
22
Fundación Jiménez Díaz, Pathology,
Madrid, Spain
TABLE: Clinical characteristics of the 24 patients with ENKTLNT at
diagnose
SUPPLEMENT ABSTRACTS
-
311
Introduction: Extranodal natural killer (NK)/Tcell lymphoma,
nasal type (ENKTLNT) is a rare and aggressive disease associated
with EpsteinBarr virus (EBV) infection. It is much more common
in Asia and Latin America, and data from European cases are
very limited. Oncogenic alterations have not been fully described
due to its rarity and the difficulties inherent to a tumor with
high necrosis and minimumsize biopsies. Treatment for ENKTLNT
lymphoma is mainly based on cytotoxic therapy, with very little
contribution of targeted therapy. The aim of this study is to
characterize the oncogenic phenotype in ENKTLNT lymphoma,
through the gene expression profile (GEP) study using a dedicated
NanoString CHIP in a series of patients diagnosed of ENKTLNT.
Patients and Methods: Eightynine patients with ENKTLNT diag-
nosed from 2000 to 2017 were identified in 24 academic centers in
Spain. After histological revision and quality control, a NanoString
gene profile could be successfully performed in 24 cases. Normalized
count data were log2 transformed and agglomerative hierarchical
clustering of gene expression were performed. The Euclidean dis-
tance was considered.
Results: Clinical characteristics at presentation of the 24 patients did
not differ from the global series. In summary, median age was 51
years, male 58%, Caucasian 58%, extranasal ENKTLNT 46%. OS at 5
y was 37% (95%CI 2750). ENKTLNT cases exhibited a cytotoxic
signature including the genes GZMA, GZMB, NKG7 and PRF1.
Additionally they showed a homogeneous expression of an EBV
signature including 4 genes expressed in both lytic and latent phases.
Tumor signatures included a strong expression of immune regulator
genes as B2M and HLAII and a coregulated gene set with AKT,
PI3KCA, IKBIB, MTOR and TGFB, revealing the increased expression
of a targetable gene pathway that associates PI3K/MTOR/AKT with
NFKB and TGFB. A proliferation signature was also found, with the
expression of Ki67, E2F1, PCNA and CDK2. The analysis included the
expression of genes for targeted therapy and revealed a high
expression of both CD274 (PDL1) and PDCD1LG2 (PDL2), a variable
expression of TNFRSF8 (CD30) and intense expression of CXCR4
and PIM1.
Conclusions: ENKTLNT cells show a distinct signature that includes
cytotoxic genes, EBVexpressed genes and immune regulator genes.
Data obtained in this analysis could support the introduction of
therapy targeting PDL1, PDL2 and PD1, together with antiCD30
therapy. Moreover, new targets have been identified, and blocking
antibodies antiCXCR4 or kinase inhibitors anti PIM1, used in clinical
trials in other indications, could also be tested in patients with
ENKTLNT.
Keywords: Aggressive Tcell nonHodgkin lymphoma
No conflicts of interest pertinent to the abstract.
228 | PERIPHERAL TCELL LYMPHOMA: MOLECULAR
PROFILING DISTINGUISHES SUBCLASSES, RECOGNIZES THE
TUMOR ARCHITECTURE AND IDENTIFIES PROGNOSTIC
MARKERS
M. Rodríguez
1
, L. TomásRoca
2
, R. AlonsoAlonso
1
, R. Manso
Alonso
2
, L. Cereceda
1
, J. Borregón
2
, T. Villaescusa
3
, Raúl Córdoba
4
,
M. SánchezBeato
5
, I. FernándezMiranda
6
, I. Betancor
2
, C. Bárcena
7
,
J. F. García
8
, M. Mollejo
9
, Món. GarcíaCosio
10
, P. MartinAcosta
11
, F.
Climent
12
, D. Caballero
13
, R. Mondéjar
14
, L. Kessler
15
, C. Scholz
15
, A.
Gualberto
15
, S. M. RodríguezPinilla
1
, M. Án. Piris
1
1
Instituto de Investigación SanitariaFundación Jiménez Díaz University
Hospital. CIBERONC. Madrid, Spain, Pathology Department, Madrid,
Spain,
2
Pathology Department, Instituto de Investigación Sanitaria
FIGURE:
Clustering genes with normalized counts of the 24 patients
with ENKTLNT
312
-
SUPPLEMENT ABSTRACTS
Fundación Jiménez Díaz University Hospital, Pathology Department,
Madrid, Spain,
3
Fundación Jiménez Díaz University Hospital, Health
Research Institute IISFJD, Madrid, Spain, Department of Hematology,
Madrid, Spain,
4
Fundación Jiménez Díaz University Hospital, Health
Research Institute IISFJD, CIBERONC, Madrid, Spain., Department of
Hematology, Madrid, Spain,
5
Instituto de Investigación Sanitaria Puerta
de HierroSegovia de Arana, CIBERONC, Madrid, Spain, Lymphoma
Research Group, Medical Oncology Department, Madrid, Spain,
6
Instituto
de Investigación Sanitaria Puerta de HierroSegovia de Arana, Madrid,
Spain, Lymphoma Research Group, Medical Oncology Department,
Madrid, Spain,
7
Hospital Universitario 12 de Octubre, Madrid, Spain,
Pathology Department, Madrid, Spain,
8
Hospital MD Anderson Cancer
Center, CIBERONC, Madrid, Spain, Pathology Department, Madrid, Spain,
9
Hospital Virgen de la Salud, CIBERONC, Toledo, Spain, Pathology
Department, Toledo, Spain,
10
Hospital Universitario Ramón y Cajal,
CIBERONC, Madrid, Spain, Pathology Department, Madrid, Spain,
11
Hospital Universitario Puerta de HierroSegovia de Arana, CIBERONC,
Madrid, Spain, Pathology Department, Madrid, Spain,
12
Hospital Uni-
versitari de Bellvitge, IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain,
Pathology Department, Barcelona, Spain,
13
Hospitalario Universitario de
Salamanca (HUS/IBSAL), Salamanca, Spain, Haematology Department,
Salamanca, Spain,
14
Hospital Universitario Virgen del Rocío, CIBERONC,
Sevilla, Spain, Laboratory, Sevilla, Spain,
15
Kura Oncology Inc., Kura
Oncology Inc., San Diego, California, USA
Introduction: Peripheral Tcell Lymphomas (PTCLs) are aggressive
tumours with unfavourable prognosis, with around 30% overall sur-
vival (OS) after 5 years. Histological and molecular studies have
revealed a striking degree of heterogeneity, with three major PTCL
subtypes defined. Consistent diagnosis and prognostication are still
difficult to achieve, because of the difficulty of reproducing results,
and the dearth of clinically applicable prognostic biological markers.
Methods: We have analyzed a series of 105 PTCL cases (66 angioim-
munoblastic Tcell lymphoma, AITL; 21 PTCLnot otherwise specified,
PTCLNOS; and 18 PTCLwith T follicular helper phenotype, PTCL
TFH) patients using a customized NanoString platform that includes
208 genes associated with Tcell differentiation, oncogenes and tumor
suppressor genes, deregulated pathways and stromal cell sub-
populations. Specifically, the platform includes genes expressed by the
multiple cell types present in PTCL specimens, together with normal T
cell populations. These are used to try and enable the deconvolution of
the Tcell lymphoma microenvironment, and thereby develop an in-
tegrated perspective on the cell composition of PTCL tumor
specimens.
Results: A comparative analysis of the various histological types of
PTCL (AITL, PTCLNOS and PTCLTFH) showed specific sets of genes
to be associated with each of the diagnoses, including TFH markers,
cytotoxic markers and genes whose expression was a surrogate for
specific cellular subpopulations, including follicular dendritic cells,
mast cells and genes belonging to specific cellsurvival pathways (NF
κB). Unsupervised analysis of the expression of the genes here
studied revealed clusters of coregulated genes that identified the
main cell components of the tumor. The analysis did not reveal any
differences in survival probability associated with the histological
subclassification, but did identify specific genes and gene sets whose
expression was associated with changes in survival probability for
each of the PTCL subtypes, independently of the clinical variables
included in the International Prognostic Index (IPI). These included a
Bcell gene set in cases of AITL, the expression of proliferation
markers in PTCLNOS, and the expression of cytotoxic markers in
cases with a diagnosis of PTCLTFH. For each PTCL lymphoma type, a
multivariate analysis identified genes that allow the series of cases to
be stratified into different risk groups. This was validated for AITL in
an independent series of 54 additional cases.
Conclusions: In summary, our study supports the current division of
PTCL into these three categories (AITL, PTCLNOS and PTCLTFH),
identifies gene sets potentially useful for this classification and rec-
ognizes the expression of Bcell genes as an IPIindependent prog-
nostic factor for AITL subtype.
EA previously submitted to regional or national meetings (up to
1000 attendees).
The research was funded by: The research was supported by grants
from Instituto de Salud Carlos III, from Ministerio de Economía,
Industria y Competitividad, Asociación Española Contra el Cáncer
(AECC), Comunidad Autónoma de Madrid and Centre for Biomedical
Network Research on Cancer (CIBERONC): SAF201347416R,
CIBERONCISCIII (CB16/12/00291), ISCIIIMINECOAESFEDER
(Plan Estatal I + D + I 20132016), ISCIIIMINECO AESFEDER
(Plan Estatal I + D + I 20172020), AECC PROYE18054PIRI, CAM
B2017/BMD3778, PIC97/2017_FJD, PIE15/0081, PI17/00272,
PIE16/01294, GILEAD (GL18/00019) and PIC 04119. L. Tomas
Roca was funded by Marie SkłodowskaCurie Individual Fellowship
(No 882597).
Keywords: Genomics, Epigenomics, and Other Omics, Diagnostic and
Prognostic Biomarkers, Aggressive Tcell nonHodgkin lymphoma
Conflicts of interests pertinent to the abstract
M. Án. Piris
Consultant or advisory role: Millenium/Takeda, Celgene, Gilead,
Jansen, NanoString, Kyowa Kirin
Research funding: Millenium/Takeda, Gilead, Kura
229 | MUTATIONAL ANALYSIS OF THE DIFFERENT NODAL
PERIPHERAL TCELL LYMPHOMA SUBCLASSES
L. TomasRoca
1
, M. Rodriguez
2
, R. AlonsoAlonso
2
, L. Cereceda
2
, S.
M. RodriguezPinilla
2
, J. Borregón
1
, R. Manso
1
, T. Villaescusa
3
, R.
Córdoba
4
, M. SánchezBeato
5
, I. FernándezMiranda
6
, C. Barcena
7
, J.
F García
8
, M. Mollejo
9
, M. GarcíaCosio
10
, P. MartinAcosta
11
, F.
Climent
12
, D. Caballero
13
, M. A. Piris
14
1
Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Pathology
Department, Madrid, Spain,
2
Instituto de Investigación Sanitaria
Fundación Jiménez Díaz, Centro de Investigación Biomédica en Red de
Cáncer (CIBERONC), Pathology Department, Madrid, Spain,
3
Hospital
SUPPLEMENT ABSTRACTS
-
313
Universitario Fundación Jiménez Díaz, Haematology Department, Madrid,
Spain,
4
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC),
Hospital Universitario Fundación Jiménez Díaz, Haematology
Department, Madrid, Spain,
5
Centro de Investigación Biomédica en Red de
Cáncer (CIBERONC), Instituto de Investigación Sanitaria Puerta de Hierro
Segovia de Arana, Medical Oncology Department, Madrid, Spain,
6
Lym-
phoma Research Group, Instituto de Investigación Sanitaria Puerta de
HierroSegovia de Arana, Medical Oncology Department, Madrid, Spain,
7
Hospital Universitario 12 de Octubre, Pathology Department, Madrid,
Spain,
8
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC),
Hospital MD Anderson Cancer Center, Pathology Department, Madrid,
Spain,
9
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC),
Hospital Virgen de la Salud, Pathology Department, Madrid, Spain,
10
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC),
Hospital Universitario Ramón y Cajal, Madrid, Pathology Department,
Madrid, Spain,
11
Centro de Investigación Biomédica en Red de Cáncer
(CIBERONC), Hospital Universitario Puerta de HierroSegovia de Arana,
Pathology Department, Madrid, Spain,
12
Hospital Universitari de Bellvitge,
IDIBELL, L’Hospitalet de Llobregat, Pathology Department, Barcelona,
Spain,
13
Hospitalario Universitario de Salamanca (HUS/IBSAL), Pathology
Department, Madrid, Spain,
14
Instituto de Investigación Sanitaria Fun-
dación Jiménez Díaz, Centro de Investigación Biomédica en Red de Cáncer
(CIBERONC), Pathology Department, Madrid, Spain
Introduction: Nodal peripheral Tcell lymphoma (PTCL) subclassifi-
cation (Angioimmunoblastic TCL, PTCLwith T Follicular Helper
phenotype and PTCLNOS) and therapeutic targeting is still contro-
versial. Overall survival (OS) is only around 30% after 5 years.
Methods: We performed targeted nextgeneration sequencing of 61
selected genes in 76 PTCL patients. Among the 76cases, 44 were
classified as AITL, 18 as PTCLTFH and 14 as PTCLNOS.
Results: Our analysis revealed a wide variety of genetic variants that
possibly drive the development of AITL, PTCLTFH and/or PTCLNOS.
We identified an average of 4 variants per patient, mainly clustered in
genes regulating chromatin conformation (TET2, DNMT3A) and Tcell
differentiation (RHOA, MTOR, IDH2, VAV1 and NOTCH1). More
frequently mutated genes were TET2 (76,31%) and DNMT3A (27,63%).
Multiple mutations were found in TET2, VAV1, RHOA, NOTCH1, MTOR,
JAK1, ZEB1, ATM, DNMT3A and ARID1B.
Main difference among the three Nodal PTCL classes was
the higher frequency of RHOA
G17V
mutations (p < 0.0001), pre-
sent approximately 2 times more frequently in AITL cases (34,09%)
than in PTCLTFH (16,66%), and they were not detected in PTCLNOS.
All three Nodal PTCL subtypes share finding suggesting Clonal
Hematopoiesis (CH) in TET2 and DNMT3A genes. Cases with higher
variant allele frequencies (VAF)s in TET2 and DNMT3A genes vs.
other mutated genes were attributed to CH. In our study we found
this phenomenon to take place in all Nodal PTCL subtypes (AITL:
31,8%; PTCLTFH: 50%; PTCLNOS: 35,71%). A correlation was not
found between specific mutations, mutational index, mutations
attributed to CH and clinical outcome.
Conclusions: There is a common molecular basis for the three Nodal
PTCL with very frequent mutations in genes regulating chromatin
conformation associated with mutations in genes governing Tcell
differentiation. RHOA G17V mutations were highly significant
enriched in AITL. Findings suggesting Clonal Hematopoiesis were
found in the three types of nodal PTCL.
The research was funded by: The research was supported by grants
from Instituto de Salud Carlos III, from Ministerio de Economía,
Industria y Competitividad, Asociación Española Contra el Cáncer
(AECC), Comunidad Autónoma de Madrid and Centre for Biomedical
Network Research on Cancer (CIBERONC): SAF201347416R,
CIBERONCISCIII (CB16/12/00291), ISCIIIMINECOAESFEDER
(Plan Estatal I + D + I 20132016), AECC PROYE18054PIRI, CAM
B2017/BMD3778, PIC97/2017_FJD, PIE15/0081, PIE16/01294 and
PI19/00715. L.TomasRoca was funded by Marie SkłodowskaCurie
Individual Fellowship (No 882597).
Keywords: Diagnostic and Prognostic Biomarkers, Pathology and
Classification of Lymphomas
Conflicts of interests pertinent to the abstract
M. A. Piris
Consultant or advisory role: Millenium/Takeda, Celgene, Gilead,
Jansen
Research funding: Millenium/Takeda, Gilead, Kura
Other remuneration: Lectures fees Millenium/Takeda, Jansen,
Nanostring, Kyowa Kirin
NEW DRUGS
230 | WITHDRAWN
231 | PRMT5 INHIBITION RESTARTS A PROAPOPTOTIC
PROGRAM AND CREATES VULNERABILITY TO COMBINATION
TREATMENT WITH BCL2 INHIBITOR VENETOCLAX IN MANTLE
CELL LYMPHOMA
F. Brown
1
, I. Hwang
2
, S. Sloan
1
, C. Hinterschied
1
, J. HelmigMason
1
,
M. Long
1
, Y. Youssef
1
, W. Chan
1
, A. Prouty
1
, J. Chung
1
, Y. Zhang
3
, S.
ChenKiang
2
, M. DiLiberto
2
, O. Elemento
4
, L. Sehgal
1
, L. Alinari
1
, P.
Scherle
3
, K. Vaddi
3
, R. Lapalombella
1
, J. Paik
2
, R. A. Baiocchi
1
1
The Ohio State University, Department of Hematology, Columbus, USA,
2
Weil Cornell Medicine, Department of Pathology and Laboratory
Medicine, New York, USA,
3
Prelude Therapeutics, R&D, Wilmington,
Delaware, USA,
4
Weil Cornell Medicine, Department of Physiology &
Biophysics, New York, New York, USA
Mantle cell lymphoma (MCL) is an incurable B cell malignancy,
comprising 5% of nonHodgkin lymphomas diagnosed annually. MCL
is associated with a poor prognosis due to emergence of resistance to
immunochemotherapy and targeted agents. The average overall
survival of patients with MCL is 46 years and for the majority of
patients who progress on targeted agents, survival remains at a
314
-
SUPPLEMENT ABSTRACTS
dismal 38 months. There is a major unmet need to identify new
therapeutic approaches that are well tolerated to improve treatment
outcomes and quality of life.
The type II protein arginine methyltransferase enzyme, PRMT5 is
overexpressed and promotes growth and survival of MCL. Inhibition
of PRMT5 with a novel, SAMcompetitive class of inhibitors drives
antitumor activity in MCL cell lines and patient derived xenograft
models derived from patients with relapse or refractory disease.
Selective inhibition of PRMT5 in these models and MCL cell lines
leads to disruption of constitutive PI3K/AKT signaling, dephosphor-
ylation and nuclear translocation of FOXO1, and enhanced recruit-
ment of this tumor suppressor protein to target genes. By performing
chromatin immunoprecipitationseq analysis, we identified over 800
newly emerged FOXO1bound genomic loci, among which pro
apoptotic BH3 family members including multiple proapoptotic
BCL2 family proteins. BAX was identified as the most common
direct target of FOXO1transriptional activity which led us to hy-
pothesize that PRMT5 inhibition could potentially drive a therapeutic
vulnerability to the BCL2 inhibitor venetoclax.
Single agent and combination treatment with venetoclax and
PRT382 was performed in nine MCL lines and IC50 and synergy
scores showed significant levels of synergy in the majority of MCL
lines tested. CCMCL1, a BCL2 negative MCL line, and Maver1,
which is highly resistant to PRMT5i, were the only cell lines to not
show synergy. The cell line with the highest levels of synergy, Z138,
expressed high levels of BCL2 and is ibrutinib resistant. Overall,
there was a strong positive correlation between BCL2 expression
and synergy score (r = 0.8956, p = 0.0064).
In vivo evaluation in two preclinical MCL models showed thera-
peutic synergy with combination venetoclax/PRT382 treatment.
Mice were treated with subtherapeutic doses of venetoclax and/or
PRT382 and disease burden was assessed weekly via flow cytometry.
Combination treatment with welltolerated doses of venetoclax and
PRMT5 inhibitors in the MCL in vivo models showed synergistic anti
tumor activity. Both PDX models showed an extension of life with
combination treatment (P < 0.001) and delayed disease progression
(P < 0.05). This preclinical data provides mechanistic rationale while
demonstrating therapeutic synergy in this preclinical study and
justifies further consideration of this combination strategy target-
ing PRMT5 and BCL2 in MCL in the clinical setting.
EA previously submitted to EHA 2021.
The research was funded by: The College of Medicine at The Ohio
State University, USA; The NIH, USA; Prelude Therapeutics, USA;
Keywords: Genomics, Epigenomics, and Other Omics, Molecular
Targeted Therapies, Combination Therapies
Conflicts of interests pertinent to the abstract
Y. Zhang
Employment or leadership position: Prelude Therapeutics
P. Scherle
Employment or leadership position: Prelude Therapeutics
K. Vaddi
Employment or leadership position: Prelude Therapeutics
R. A. Baiocchi
Consultant or advisory role: Prelude Therapeutics
Research funding: Prelude Therapeutics
232 | CC99282 IS A NOVEL CEREBLON E3 LIGASE
MODULATOR (CELMOD) AGENT WITH POTENT AND BROAD
ANTITUMOR ACTIVITY IN PRECLINICAL MODELS OF DIFFUSE
LARGE BCELL LYMPHOMA (DLBCL)
A. LopezGirona
1
, L. Groocock
1
, Z. Mo
1
, R. K. Narla
1
, P. Janardhanan
1
,
S. Wood
1
, D. Mendy
1
, L. Barnes
1
, S. Peng
1
, D. Jankeel
1
, C. Fontanillo
2
,
S. Carrancio
1
, J. Hansen
3
1
Bristol Myers Squibb, Oncogenesis Therapeutic Research Center,
Princeton, New Jersey, USA,
2
Bristol Myers Squibb, Informatics and
Predictive Sciences, Princeton, New Jersey, USA,
3
Bristol Myers Squibb,
Small Molecule Drug Discovery, Princeton, New Jersey, USA
Introduction: CC99282 is an Ikaros and Aiolostargeting oral
CELMoD agent in development for the treatment of relapsed/re-
fractory nonHodgkin lymphomas (R/R NHL). While patients with R/
R NHL tend to have poor prognoses, agents mediating Ikaros/Aiolos
degradation, such as lenalidomide (LEN) and avadomide (AVA), have
shown promise in the R/R NHL setting.
Methods: The effects of CC99282 were studied in lymphoma and
nontumorigenic human cell lines, primary cells, and lymphoma
xenograft models. Shotgun proteomics, immunoblotting, enzyme
fragment complementation assays, and flow cytometry studies
assessed substrate degradation selectivity of CC99282. CRISPR/
Cas9 gene editing was performed in lymphoma cell lines and a Tcell
restimulation assay evaluated immunestimulatory effects.
Results: CC99282 demonstrated potent autonomous cell killing and
apoptosis in DLBCL cells, independent of the origin subtype, pres-
ence of highrisk chromosomal translocations, or acquired resistance
to doxorubicin. Of 23 cell lines tested, 20 showed sensitivity to CC
99282 with IC
50
of 1–500 nM; similar low IC
50
values were achieved
only in 3 cell lines treated with AVA and none with LEN. No general
cytotoxicity was observed in nontumorigenic cells in culture treated
with 10 µM of CC99282. While genetic knockout of either IKZF1/
Ikaros or IKZF3/Aiolos sensitized DLBCL cells, the expression of
degradationresistant mutants of Ikaros/Aiolos protected them from
the antiproliferative effects of CC99282. The deep and sustained
degradation of Ikaros/Aiolos in DLBCL cells treated with CC99282
correlated with: the induction of interferon (IFN)inducible genes
(IRF7, IFIT3, and DDX58); a reduction of the highly critical oncogenic
factors cMyc and IRF4; and the induction of cleaved caspases and
PARP.
Several DLBCL xenograft models treated with CC99282 (1–30
mg/kg) at different dosing schedules showed significant (P < 0.0001)
SUPPLEMENT ABSTRACTS
-
315
tumor regression and tumorfree status (Figure). The strong anti-
tumor activity was accompanied with robust distribution of CC
99282 across multiple tissues, including effectively crossing the
bloodbrain barrier in the intracranial xenograft model of central
nervous system lymphoma.
Degradation of Ikaros/Aiolos by CC99282 in T cells correlated
with increased secretion of IL2, a hallmark of immune activation.
CC99282 was able to reverse Tcell exhaustion and induce secretion
of the effector cytokines/chemokines GMCSF, IFNγ, and TNFα, at
concentrations (0.1–100 nM) that induced strong antitumor effects
in vitro.
Conclusions: CC99282 is a novel CELMoD that, compared with LEN
and other immunomodulatory agents, shows enhanced anti-
proliferative, apoptotic, and immunestimulatory activity in a range of
DLBCL models, including those with acquired chemoresistance.
These data support the clinical investigation of CC99282 in patients
with R/R NHL.
FIGURE:
ANTITUMOR ACTIVITY OF CC99282 IN A WSUDLCL2
DLBCL XENOGRAFT MODEL. FEMALE SCID MICE, INOCULATED
WITH 10 10
6
WSUDLCL2 TUMORC CELLS INTO THE FLANK,
WHERE RANDOMIZED INTO TREATMENT GROUPS (N = 9/GROUP)
AT TREATMENT INITIATION. TEST ARTICLE TREATMENT STARTED
ON D18 WHEN TUMORS WHERE APPROXIMATELY 350 MM
3
. THE
5D ON/2D OFF REPRESENTS QD DOSING FOR 5 CONSECUTIVE
DAYS FOLLOWED BY 2 DAYS OFF. THE CHOP SINGLECYCLE
SCHEDULE ENTAILED CYCLOPHOSPHAMIDE (40 MG/KG),
DOXORUBICIN (3.3 M/KG), ADMINISTERED PO ON D 15 BEGIN-
NING ON D1 OF TREATMENT. RESULTS ARE PRESENTED AS MEAN
VALUES WITH ERROR BARS REPESENTS TUMOR FREE. CHOP,
CYCLOPHOSPHAMIDE DOXORUBICIN, VINBLASTINE, AND
PREDNISONE; D,DAY; DLBCL, DIFFUSE LARGE BCELL LYM-
PHOMA; IV, INTRAVENOUSLY; PO, ORALLY; QD, DAILY; SEM,
STANDARD ERROR OF THE MEAN
The research was funded by: Bristol Myers Squibb
Keywords: Molecular Targeted Therapies
Conflicts of interests pertinent to the abstract
A. LopezGirona
Employment or leadership position: Bristol Myers Squibb
Stock ownership: Bristol Myers Squibb
L. Groocock
Employment or leadership position: Bristol Myers Squibb
Stock ownership: Bristol Myers Squibb
Z. Mo
Employment or leadership position: Bristol Myers Squibb
Stock ownership: Bristol Myers Squibb
R. K. Narla
Employment or leadership position: Bristol Myers Squibb
Stock ownership: Bristol Myers Squibb
P. Janardhanan
Employment or leadership position: Bristol Myers Squibb
Stock ownership: Bristol Myers Squibb
S. Wood
Employment or leadership position: Bristol Myers Squibb
Stock ownership: Bristol Myers Squibb
D. Mendy
Employment or leadership position: Bristol Myers Squibb
L. Barnes
Employment or leadership position: Bristol Myers Squibb
S. Peng
Employment or leadership position: Bristol Myers Squibb
D. Jankeel
Employment or leadership position: Bristol Myers Squibb
Stock ownership: Bristol Myers Squibb
C. Fontanillo
Employment or leadership position: Bristol Myers Squibb
Stock ownership: Bristol Myers Squibb
S. Carrancio
Employment or leadership position: Bristol Myers Squibb
Stock ownership: Bristol Myers Squibb
J. Hansen
Employment or leadership position: Bristol Myers Squibb
233 | CFT7455: A NOVEL, IKZF1/3 DEGRADER THAT
DEMONSTRATES POTENT TUMOR REGRESSION IN A SPECTRUM
OF NHL XENOGRAFT MODELS
S. Perino
1
, B. Class
1
, C. Henderson
1
, M. Isasa
1
, R. J. Kirby
1
, R. V.
Agafonov
1
, P. Chaturvedi
1
, S. J. Eron
1
, A. Good
1
, A. A. Hart
1
, J. A.
316
-
SUPPLEMENT ABSTRACTS
Henderson
1
, B. T. Kreger
1
, M. Mahler
1
, R. M. Pollock
1
, A. S. Crystal
1
,
C. G. Nasveschuk
1
, S. L. Fisher
1
, D. A. Proia
1
1
C4 Therapeutics, Discovery, Watertown, Massachusetts, USA
Introduction: Ikaros family zinc finger protein 1 and 3 (IKZF1/3) are
essential transcription factors (TF) for differentiation of B and T
lymphocytes. IMiDs (e.g. pomalidomide (pom)) degrade IKZF1/3 via
interaction with the cereblon (CRBN) E3 ligase and have shown
promise in NHL. Preclinical data suggest improvements in IKZF1/3
degraders may lead to enhanced efficacy. CFT7455 is a novel IKZF1/
3 degrader optimized for high affinity CRBN binding and IKZF1/3
degradation, resulting in downregulation of the interferon regulatory
factor 4 (IRF4), a critical regulator in nonHodgkin's lymphoma
(NHL), including diffuse large Bcell lymphoma (DLBCL), mantle cell
lymphoma (MCL) and peripheral Tcell lymphoma (PT).
Methods: Protein expression in cell lines and tumor xenografts were
quantified by immunoassays or targeted mass spectrometry. Binding
affinity was determined by fluorescence polarization or cellular
NanoBRET assays. Cell viability were monitored by CellTiterGlo.
Tumor xenograft studies were conducted by implanting human NHL
lines into immunocompromised mouse strains.
Results: CFT7455's potency as a CRBN binder is evident from cellular
CRBN competition studies (IC50 = 0.4 nM). In the ALK+ anaplastic
large cell lymphoma (ALCL) line KiJK, CFT7455 treatment led to >80%
degradation of IKZF1, which was blocked by proteasome or NEDD8
inhibition, demonstrating on mechanism activity. CFT7455 demon-
strated potent antiproliferative activity across a panel of NHL cell lines.
In KiJK xenografts, pom treatment was ineffective at a clinically
relevant dose (3000 µg/kg/day). CFT7455 treatment (100 µg/kg/day,
PO) resulted in durable tumor regression associated with deep IKZF3
degradation and IRF4 downregulation (7% and 25% remaining,
respectively). CFT7455 showed dose dependent efficacy in the ALK
ALCL xenograft model, DL40, from 3100 µg/kg with regressions at
doses 10 µg/kg. Global proteomic studies on DL40 xenografts
treated with CFT7455 (100 µg/kg, 4 hours) showed only IKZF1/3
were significantly degraded.
MCL is characterized by elevated cyclin D1, subsequent release
of E2F1 and pathway activation. In the REC1 MCL xenograft model,
doses of CFT7455 10 µg/kg promoted tumor regression. Pharma-
codynamic studies showed that CFT7455 (30 µg/kg) promoted
degradation of IKZF3 and downregulation of cyclin D1 and E2F1.
In a pom insensitive DLBCL model (TMD8), administration of
CFT7455 (100 µg/kg) led to tumor regression. Together these results
show that the optimized CRBN binding and catalytic activity of
CFT7455 results in rapid, deep and sustained degradation of IKZF1/3
and translates to tumor regressions in NHL models.
Conclusions: CFT7455 is a potent, selective catalytic degrader of
IKZF1/3, with single agent antitumor activity in DLBCL, ALCL, and
MCL models including those insensitive to pom. These results sup-
port clinical investigation of CFT7455 for NHL.
Keywords: Molecular Targeted Therapies, Aggressive Bcell non
Hodgkin lymphoma, Aggressive Tcell nonHodgkin lymphoma
Conflicts of interests pertinent to the abstract
S. Perino
Employment or leadership position: C4 Therapeutics
Stock ownership: C4 Therapeutics
B. Class
Employment or leadership position: C4 Therapeutics
Stock ownership: C4 Therapeutics
C. Henderson
Employment or leadership position: C4 Therapeutics
Stock ownership: C4 Therapeutics
M. Isasa
Employment or leadership position: C4 Therapeutics
Stock ownership: C4 Therapeutics
R. J. Kirby
Employment or leadership position: C4 Therapeutics
Stock ownership: C4 Therapeutics
R. V. Agafonov
Employment or leadership position: C4 Therapeutics
Stock ownership: C4 Therapeutics
P. Chaturvedi
Employment or leadership position: C4 Therapeutics
Stock ownership: C4 Therapeutics
S. J. Eron
Employment or leadership position: C4 Therapeutics
Stock ownership: C4 Therapeutics
A. Good
Employment or leadership position: C4 Therapeutics
Stock ownership: C4 Therapeutics
A. A. Hart
Employment or leadership position: C4 Therapeutics
Stock ownership: C4 Therapeutics
J. A. Henderson
Employment or leadership position: C4 Therapeutics
Stock ownership: C4 Therapeutics
B. T. Kreger
Employment or leadership position: C4 Therapeutics
Stock ownership: C4 Therapeutics
M. Mahler
Employment or leadership position: C4 Therapeutics
Stock ownership: C4 Therapeutics
R. M. Pollock
Employment or leadership position: C4 Therapeutics
Stock ownership: C4 Therapeutics
SUPPLEMENT ABSTRACTS
-
317
A. S. Crystal
Employment or leadership position: C4 Therapeutics
Stock ownership: C4 Therapeutics
C. G. Nasveschuk
Employment or leadership position: C4 Therapeutics
Stock ownership: C4 Therapeutics
S. L. Fisher
Employment or leadership position: C4 Therapeutics
Stock ownership: C4 Therapeutics
D. A. Proia
Employment or leadership position: C4 Therapeutics
Stock ownership: C4 Therapeutics
234 | GLYCOPROTEIN PTGDS ACTS AS A POTENTIAL TARGET
IN DIFFUSE LARGE BCELL LYMPHOMA BY REGULATING MYH9
WNT‐β‐CATENIN/STAT3 AXIS
S. Hu
1
, X. Zhou
1
, S. Ren
1
, Y. Cai
1
, J. Liu
1
, Y. Han
1
, Y. Zhao
1
, J. Yang
1
,
X. Wang
1
1
Shandong Provincial Hospital Affiliated to Shandong University,
Department of Hematology, Jinan, China
Introduction: Glycoprotein prostaglandin D2 Synthase (PTGDS) is a
member of lipocalin superfamily and AT56 is its selective inhibitor.
PTGDS has been involved in several cellular processes, yet its func-
tion and mechanism in carcinogenesis remains ill defined. Herein, we
aimed to investigate the functional significance of PTGDS and pro-
posed a novel therapeutic strategy in diffuse large Bcell lymphoma
(DLBCL).
Methods: Lymph node biopsies from 53 DLBCL patients and 28
reactive hyperplasia cases were obtained with informed consents.
CD19
+
magnetic microbeads were used to purify CD19
+
B cells.
Lentivirus tranfection was performed to stably knockdown or over-
express PTGDS. CoIP and mass spectrometry were used to investi-
gate molecular mechanism. Glycosylation sites were verified by point
mutations. Xenograft model was established and BALB/c nude mice
were imaged using InVivo small animal imaging system.
Results: Bioinformatics analysis showed that PTGDS was upregu-
lated in DLBCL based on Oncomine database. High expression of
PTGDS protein was found in DLBCL tissues and serum, which was
correlated with poor prognosis.
PTGDS overexpression and rhPTGDS caused increased cell
proliferation. PTGDS knockdown and AT56 significantly inhibited cell
proliferation and invasion, promoted cell cycle arrest and cell
apoptosis. PTGDS inhibition also enhanced sensitivity to Bend-
amustine and Adriamycin. Besides, in vivo studies showed PTGDS
knockdown and AT56 exerted antitumor effect in DLBCL.
PTGDS was found to interact with oncogenic factor, MYH9
through CoIP and mass spectrometry. The expression of MYH9 was
decreased by PTGDS inhibition, which also inhibited activation of
Wnt‐β‐catenin/STAT3 pathway. Besides, Wnt3a could rescue the
inhibitory role of AT56 on malignant behaviors, including cell pro-
liferation, cell cycle arrest and cell apoptosis. Moreover, the effect of
AT56 on Wnt pathway could also be reversed by Wnt3a. WP1066
could reverse enhanced proliferation caused by PTGDS over-
expression, and the inhibited proliferation and increased apoptosis
caused by AT56 were enhanced by WP1066. Both the proliferation
promotion and the activation of Wnt‐β‐catenin/STAT3 pathway by
PTGDS overexpression was restored by Blebbistatin.
The Nglycosylation of PTGDS protein in Asn 51 and Asn78 was
verified and abnormal glycosylation resulted in nuclear translocation,
prolonged half time and enhanced oncogenic role.
Conclusions: Our data firstly identified the oncogenic role of
PTGDS in DLBCL. High PTGDS expression was associated with
prognosis of DLBCL patients. Moreover, in vitro and in vivo studies
indicated that PTGDS inhibition exerted antitumor effect by
regulating MYH9Wnt‐β‐catenin/STAT3 axis. This study indicates
that PTGDS acts as a potential molecular target for DLBCL
treatment and highlights the potential role of AT56 as a novel
therapeutic strategy for DLBCL.
The research was funded by: National Natural Science Foundation
(No.82070203, No.81770210, No.81473486 and No.81270598); Key
Research and Development Program of Shandong Province
(No.2018CXGC1213); Technology Development Projects of
FIGURE 1
318
-
SUPPLEMENT ABSTRACTS
Shandong Province (No.2017GSF18189); Translational Research
Grant of NCRCH (No.2021WWB02, No.2020ZKMB01); Taishan
Scholars Program of Shandong Province; Shandong Provincial Engi-
neering Research Center of Lymphoma; Academic Promotion Pro-
gramme of Shandong First Medical University (No. 2019QL018).
Keywords: Genomics, Epigenomics, and Other Omics,
Molecular Targeted Therapies, Aggressive Bcell nonHodgkin
lymphoma
No conflicts of interest pertinent to the abstract.
FIGURE 3
FIGURE 2
FIGURE 4
SUPPLEMENT ABSTRACTS
-
319
235 | CLINICAL APPLICATION OF AN EXVIVO PLATFORM TO
GUIDE THE CHOICE OF DRUG COMBINATIONS IN RELAPSED/
REFRACTORY LYMPHOMA; A PROSPECTIVE STUDY
S. De Mel
1
, J. Goh
2
, M. B. M. A. Rashid
3
, X. Y. Zhang
2
, P. Jaynes
2
, X. Liu
1
,
L. Poon
1
, E. Chan
1
, J. Lee
1
, Y. L. Chee
1
, L. P. Koh
1
, L. K. Tan
4
, T. G. Soh
4
, Y.
C. Yuen
5
, HoiY. Loi
6
, SiokB. Ng
7
, X. Goh
8
, D. Tan
9
, D. M. Z. Cheah
10
, W.
L. Pang
10
, D. Huang
10
, J. Y. Chan
11
, N. Somasundaram
11
, T. Tang
11
, S. T.
Lim
11
, C. K. Ong
12
, W.J. Chng
1
, E. K. Chow
2
, A. D. Jeyasekharan
1
1
National University Health System, Department of Haematology
Oncology, National University Cancer Institute, Singapore, Singapore,
Singapore,
2
National University of Singapore, Cancer Science Institute of
Singapore, Singapore, Singapore,
3
KYAN Therapeutics, Singapore,
Singapore,
4
National University Hospital, Department of Laboratory
Medicine, Singapore, Singapore,
5
National University Health System,
Department of Pharmacy, Singapore, Singapore,
6
National University
Hospital Singapore, Department of Diagnostic Imaging, Singapore,
Singapore,
7
National University of Singapore, Department of Pathology,
Yong Loo Lin School of Medicine, Singapore, Singapore,
8
National Uni-
versity Hospital, Department of Otorhinolaryngology, Singapore,
Singapore,
9
Mt Elizabeth Hospital, Dr Daryl Tan Clinic for Lymphoma,
Myeloma and Blood Disorders, Singapore, Singapore,
10
National Cancer
Centre Singapore, Lymphoma Genomic Translational Research Labora-
tory, Division of Cellular and Molecular Research, Singapore, Singapore,
11
National Cancer Centre Singapore, Division of Medical Oncology,
Singapore, Singapore,
12
National Cancer Centre Singapore, Division of
Cellular and Molecular Research, Singapore, Singapore
Introduction: While combination therapy is the standard of care for
relapsed/ refractory nonHodgkin lymphoma (RRNHL), the choice of
combinations for an individual patient is empirical, and response rates
remain poor. Here we explore the use of a hybrid experimental/ana-
lytic method termed Quadratic Phenotypic Optimization Platform
(QPOP), for prediction of optimal drug combinations from limited
clinical material. This highthroughput platform identifies optimal
drugcombinations on exvivo biopsies using an orthogonal array
composite design to maximise search space. These features are
potentially useful to assess personalized efficacious combinations
among a set of drugs with single agent preclinical or clinical activity in
lymphoma.
Methods: We performed a prospective cohort study of QPOP analysis
in RRNHL. Participants included RRNHL patients across two tertiary
oncology centres in Singapore, with disease amenable to biopsy or
blood/ marrow aspiration, recruited between 1
st
November 2017 and
7
th
August 2020 with a median follow up of 20 months. QPOP drug
combination scores were derived from lymphoma samples (approxi-
mately 1,000,000 cells/ patient) using a matrix of drugs with known
preclinical or clinical efficacy against NHL. Results were shared with
the treating physician, and offlabel QPOPguided therapy was offered
in the absence of standard options. The primary outcomes were
feasibility and turnaround time of QPOP analysis. The secondary
outcomes were identification of recurrent 2 and 3 drugcombinations,
and concordance of QPOP results with clinical responses.
Results: In this interim analysis period, we recruited 36 patients
comprising 19 BNHL, 15 T/NKNHL and 2 composite lymphomas
(CL), with a median age of 57.5 years and median 2 prior lines of
FIGURE 6
FIGURE 5
320
-
SUPPLEMENT ABSTRACTS
treatment. Successful QPOP analysis (Z’ score >0.5) was feasible in
31/36 cases with an average turnaround time of 5.7 (±2.1) days.
QPOP predicted frequent sensitivities to Copanlisibbased combina-
tions in BNHL (n = 7/12), and Romidepsinbased combinations in T/
NKNHL (4/11). Importantly, efficacy of specific combinations was not
entirely dependent on single agent dose responses. Clinical responses
after standardofcare (n = 15) or QPOPderived regimens (n = 5) was
evaluable for 20 independent treatments in 17/31 patients. QPOP
had a positive predictive value of 100% and a negative predictive
value of 80% for response (n = 20, p = 0.008), and an AUC of 0.838
(95%CI 0.6261.051; p = 0.011). Complete responses were achieved
with novel drug combinations, including PalbociclibEverolimus for B
NHL and RomidepsinBortezomib for T/NKNHL.
Conclusions: Prediction of sensitivity to drugcombinations in a clini-
cally applicable timeframe is feasible for RRNHL cases
through QPOP analysis. QPOP was also able to identify novel clinically
effective combinations in patients refractory to standard therapy.
The research was funded by: Funding for all aspects of the project
was provided by the Singapore Ministry of Health's National Medical
Research Council 'Singapore lYMPHoma translatiONal studY (SYM-
PHONY)' Open Fund Large Collaborative Grant (MOH00020503).
Keywords: Combination Therapies, Aggressive Bcell nonHodgkin
lymphoma, Aggressive Tcell nonHodgkin lymphoma
Conflicts of interests pertinent to the abstract
S. De Mel
Other remuneration: SDM is an inventor on a patent for QPOP titled
‘Method For Predicting A Suitable Therapy’ (Patent Cooperation
Treaty (PCT) Application No.: PCT/SG2020/050595).
M. B. M. A. Rashid
Other remuneration: MBMAR is an inventor on a patent for QPOP
titled ‘Method For Predicting A Suitable Therapy’ (Patent Coopera-
tion Treaty (PCT) Application No.: PCT/SG2020/050595).
W.J. Chng
Honoraria: Amgen, J&J, Celgene, BMS, Abbvie, Novartis, Takeda
Research funding: J&J, Celgene, Hummingbird
Other remuneration: WJC is an inventor on a patent for QPOP titled
‘Method For Predicting A Suitable Therapy’ (Patent Cooperation
Treaty (PCT) Application No.: PCT/SG2020/050595)
E. K. Chow
Employment or leadership position: KYAN Therapeutics
Stock ownership: KYAN Therapeutics
Other remuneration: EKC is an inventor on a patent for QPOP titled
‘Method For Predicting A Suitable Therapy’ (Patent Cooperation
Treaty (PCT) Application No.: PCT/SG2020/050595).
A. D. Jeyasekharan
Consultant or advisory role: Turbine Ltd, AstraZeneca, Janssen and
MSD
Research funding: Janssen and AstraZeneca.
Educational grants: Perkin Elmer
Other remuneration: ADJ is an inventor on a patent for QPOP titled
‘Method For Predicting A Suitable Therapy’ (Patent Cooperation
Treaty (PCT) Application No.: PCT/SG2020/050595).
236 | TG1701, A SELECTIVE BRUTON TYROSINE KINASE (BTK)
INHIBITOR, AS MONOTHERAPY AND IN COMBINATION WITH
UBLITUXIMAB AND UMBRALISIB (U2) IN PATIENTS WITH BCELL
MALIGNANCIES
C. Y. Cheah
1
, W. Jurczak
2
, M. Lasica
3
, N. Wickham
4
, T. Wróbel
5
, J.
Walewski
6
, C. K. Yannakou
7
, S. Cheung
4
, K. L. Lewis
1
, M. Długosz
Danecka
2
, K. Giannopoulos
8
, H. P. Miskin
9
, J.P. Tang
9
, E. Normant
9
,
O. A. O'Connor
9
, A. D. Ricart
9
, C. S. Tam
3
1
Sir Charles Gairdner Hospital, Department of Haematology, Perth,
Australia,
2
Maria SklodowskaCurie National Research Institute of
Oncology, Oncology Center, Krakow, Poland,
3
St. Vincent Hospital and
University of Melbourne, Haematology, Melbourne, Australia,
4
Ashford
Cancer Centre Research, Hematology, Adelaide, Australia,
5
Wroclaw
Medical University, Department of Haematology, Blood Neoplasms and
Bone Marrow Transplantation, Wroclaw, Poland,
6
Maria Sklodowska
Curie National Research Institute of Oncology, Department of Lymphoid
Malignancy, Warsaw, Poland,
7
Epworth HealthCare, Department of Mo-
lecular Oncology and Cancer Immunology, East Melbourne, Australia,
8
St
John's Cancer Centre, Hematology Department, Lublin, Poland,
9
TG
Therapeutics, Oncology, New York, USA
Introduction: TG1701 is a selective, covalent BTK inhibitor
administered once daily (QD). Both the “U2” combination (antiCD20
mAb ublituximab + the PI3Kδ‐CK1ε inhibitor umbralisib) and BTK
inhibition are highly active in treatmentnaïve (TN) and relapsed/
refractory (R/R) CLL, each having previously demonstrated
superiority over standard chemoimmunotherapy. Herein we report
the results of the dose escalation of TG1701 monotherapy and TG
1701+U2.
Methods: Patients (pts) with R/R CLL, MCL and Waldenström's (WM)
were enrolled in an ongoing Ph 1 study initially evaluating dose
escalation (DE) of oral TG1701 QD continuously administered in 28
day cycles (100, 200, 300, and 400 mg). After characterizing the
safety profile of TG1701 monotherapy, we implemented a parallel
DE arm of TG1701+U2. Select dose levels of TG1701 monotherapy
were expanded. All pts were treated until disease progression, un-
acceptable toxicity, or investigator/patient decision to withdraw.
Results: As of 03 February 2021, 123 pts were treated with TG
1701 as follows: 25 in the monotherapy DE arm, 61 in the 200
mg diseasespecific cohorts (20 CLL [5 TN], 21 MCL [4 TN], 20
WM [8 TN]), 20 in the 300 mg CLL cohort (4 TN), and 17 in the
1701+U2 DE arm. The median # of prior therapies was 1 (range, 1
10). All pts were BTKinaïve. All 123 pts were evaluable for
safety. TG1701 was well tolerated and the maximum tolerated
dose (MTD) for monotherapy was not reached at 400 mg
(demonstrating near 100% saturation of the BTK at all dose levels
studied). Treatment emergent adverse events (TEAE) of clinical
SUPPLEMENT ABSTRACTS
-
321
interest included atrial fibrillation (AF 4.0% of pts, G 3 in 1 case),
G 3 hypertension (2.4%), and bleeding events (18.7%, all G12).
No cases of ventricular tachyarrhythmia were reported. TEAEs
leading to TG1701 dose reduction occurred in 6.5% of pts. TEAEs
leading to treatment discontinuation occurred in 1.6% of pts (AF,
COVID19). At the data cutoff, 119 pts were evaluable for
response, including 40 in DE (Table). The median duration of
response has not been reached among responders overall. The
median followup (mFU range) was 15.9 mos (1.3 28.6+) in DE
and 8.5 mos (1.4 15.6+) in diseasespecific cohorts. Best change
from baseline in tumor burden in pts in the 1701+U2 combination
arm is presented in the figure below.
Conclusions: TG1701 exhibits an encouraging safety and efficacy
profile. The combination of 1701+U2 has been well tolerated and
dose escalation continues. The combination shows enhanced depth of
response over TG1701 monotherapy. Recruitment to this study
(NCT03671590) continues.
EA previously submitted to EHA 2021.
The research was funded by: TG Therapeutics Inc.
Keywords: Chronic Lymphocytic Leukemia (CLL), Molecular Targeted
Therapies, Combination Therapies
Conflicts of interests pertinent to the abstract
C. Y. Cheah
Employment or leadership position: None
Consultant or advisory role: JanssenCilag, Roche/Genentech, TG
Therapeutics, Loxo/Lilly, Gilead Sciences, AstraZeneca, BristolMyers
Squibb, Ascentage Pharma, MDS
Stock ownership: None
Honoraria: Roche/Genentech, JanssenCilag, TG Therapeutics, Loxo/
Lilly, AstraZeneca, BristolMyers Squibb, Gilead Sciences, Ascentage
Pharma, MDS
Research funding: Roche, Celgene, AbbVie
Other remuneration: Travel, Accommodations, Expenses: Roche
W. Jurczak
Employment or leadership position: None
Consultant or advisory role: MEI Pharma, Debiopharm, Loxo, Takeda,
AstraZeneca, BeiGene
Stock ownership: None
Honoraria: None
Research funding: GlaxoSmithKline You Acerta Pharma You Astra-
Zeneca You Nordic Nanovector You Incyte You DebiopGenentech,
Janssen, Loxo, MEI Pharma, MorphoSys, Takeda, TG Therapeutics,
BeiGene
Educational grants: None
Other remuneration: None
T. Wróbel
Employment or leadership position: None
Consultant or advisory role: Roche/Genentech, Abbvie, Takeda,
Novartis, JanssenCilag, Amgen
Stock ownership: None
Honoraria: Celgene, Roche, Gilead Sciences, Amgen, JanssenCilag
Research funding: Roche
Educational grants: None
Other remuneration: None
J. Walewski
Employment or leadership position: None
Consultant or advisory role: Roche, Abbvie, Takeda/Millennium,
Gilead Sciences, Novartis
Stock ownership: None
Honoraria: Roche, Abbvie, Servier, Amgen, Takeda/Millennium,
Gilead Sciences, Novartis
Research funding: None
Educational grants: Roche
Other remuneration: None
S. Cheung
Employment or leadership position: None
Consultant or advisory role: Novartis
Stock ownership: None
Honoraria: None
Research funding: None
Educational grants: None
Other remuneration: None
K. L. Lewis
Employment or leadership position: None
Consultant or advisory role: Roche
Stock ownership: None
TABLE Response per investigator review by treatment group
DE arm
(N = 23)
200 mg CLL
(N = 20)
200 mg MCL
(N = 20)
200 mg WM
(N = 20)
300 mg CLL
(N = 19)
1701+U2 DE arm
(N = 17)
ORR, % 56.5 95.0 60.0 95.0 100 82.3
CR, % 0 0 0 0 0 23.5
Very good PR, % 4.3 0 5.9
PR, % 47.8 95.0 60.0 70.0 100 52.9
Minor response, % 4.3 25.0 0
mFU mos 17.5 11.6 8.2 9.7 5.8 14.3
322
-
SUPPLEMENT ABSTRACTS
Honoraria: Janssen, Novartis
Research funding: None
Educational grants: Janssen, Novartis
Other remuneration: None
M. DługoszDanecka
Employment or leadership position: None
Consultant or advisory role: Servier, Abbvie
Stock ownership: None
Honoraria: None
Research funding: None
Educational grants: None
Other remuneration: Speakers' Bureau: Janssen, Servier, Roche,
Takeda.
K. Giannopoulos
Employment or leadership position: None
Consultant or advisory role: Abbvie, BristolMyers Squibb/Celgene,
Sanofi, Takeda, Amgen
Stock ownership: None
Honoraria: Janssen, BristolMyers Squibb/Celgene, Sanofi, Takeda,
Amgen.
Research funding: TG Therapeutics, Abbvie, BristolMyers Squibb/
Celgene, Sanofi, Takeda, Amgen.
Educational grants: None
Other remuneration: None
H. P. Miskin
Employment or leadership position: TG Therapeutics
Consultant or advisory role: None
Stock ownership: TG Therapeutics
Honoraria: None
Research funding: None
Educational grants: TG Therapeutics
Other remuneration: None
J.P. Tang
Employment or leadership position: TG Therapeutics
Consultant or advisory role: None
Stock ownership: TG Therapeutics, Roche, Alexion Pharmaceuticals
Honoraria: None
Research funding: None
Educational grants: None
Other remuneration: None
E. Normant
Employment or leadership position: TG Therapeutics
Consultant or advisory role: None
Stock ownership: TG Therapeutics, Surface Oncology
Honoraria: None
Research funding: None
Educational grants: None
Other remuneration: None
O. A. O'Connor
Employment or leadership position: TG TherapeuticsTG, Kymera,
NomoCan
Consultant or advisory role: Kymera, Celgene, Mundipharma,
SERVIER
Stock ownership: TG Therapeutics, Kymera.
Honoraria: Kymera, Celgene, Astex Pharmaceuticals
Research funding: Celgene, Astex Pharmaceuticals, Merck
Educational grants: None
Other remuneration: None
A. D. Ricart
Employment or leadership position: TG Therapeutics
Consultant or advisory role: None
Stock ownership: Pfizer, Merck, TG Therapeutics, Seattle Genetics,
Collegium, Immunomedics, Stemline Therapeutics
Honoraria: None
Research funding: None
Educational grants: None
Other remuneration: None
C. S. Tam
Employment or leadership position: None
Consultant or advisory role: Janssen, Loxo, Roche, BeiGene, Abbvie
Stock ownership: None
Honoraria: JanssenCilag, Abbvie, Novartis, Beigene, Pharmacyclics
Research funding: JanssenCilag, Abbvie
Educational grants: None
Other remuneration: None
237 | FIRSTMIND: A PHASE IB, OPENLABEL, RANDOMIZED
STUDY TO ASSESS SAFETY OF TAFASITAMAB OR TAFASITAMAB
+ LENALIDOMIDE IN ADDITION TO RCHOP IN PATIENTS WITH
NEWLY DIAGNOSED DLBCL
D. Belada
1
, K. Kopeckova
2
, J. M. Bergua Burgues
3
, M. André
4
, E.
Pérez Persona
5
, P. Pichler
6
, P. Klöpfer
7
, B. Brackertz
8
, E. Lohrmann
8
,
A. Lahiry
9
, N. Shah
9
, W. Brugger
7
, J. M. Burke
10
, G. S. Nowakowski
11
1
University Hospital and Faculty of Medicine, 4th Department of Internal
Medicine Hematology, Hradec Králové, Czech Republic,
2
2nd Faculty of
Medicine, Charles University and Motol University Hospital, Department
of Oncology, Prague, Czech Republic,
3
Hospital San Pedro de Alcantara,
Hematology, Cáceres, Spain,
4
Université Catholique de Louvain,
Department of Haematology, CHU UCL Namur, Yvoir, Belgium,
5
Osakidetza Basque Health Service, Araba University Hospital,
Hematology, Vitoria Gasteiz, Spain,
6
University Hospital of St.
Pölten, Department of Internal Medicine, St. Pölten, Austria,
7
MorphoSys
AG, Clinical Development, Planegg, Germany,
8
MorphoSys AG, Global
Patient Safety, Planegg, Germany,
9
MorphoSys AG, Biostatistics and Data
Management, Planegg, Germany,
10
US Oncology Research and Rocky
Mountain Cancer Centers, Hematology, Aurora, Colorado, USA,
11
Mayo
Clinic, Division of Hematology, Rochester, MN, USA
SUPPLEMENT ABSTRACTS
-
323
Introduction: Tafasitamab is a humanized, Fcmodified, antiCD19
monoclonal antibody that enhances antibodydependent cellular
cytotoxicity and phagocytosis. It is FDAapproved in combination
with lenalidomide (LEN) for adult patients (pts) with relapsed/re-
fractory diffuse large Bcell lymphoma (R/R DLBCL) ineligible for
autologous stem cell transplant. FirstMIND (NCT04134936) is a
Phase Ib, openlabel, randomized study to assess the safety and
preliminary efficacy of tafasitamab + RCHOP or tafasitamab + LEN
+ RCHOP in pts with newly diagnosed DLBCL.
Methods: Eligible pts were 18 years old, treatment (Tx)naïve,
with DLBCL, international prognostic index (IPI) 2–5 and ECOG
performance status (PS) 0–2. Pts with known double or triplehit
and transformed lymphoma were excluded. Tx included six 21day
[D] cycles of RCHOP + tafasitamab (12 mg/kg IV, D1, 8, 15) (arm
A) or RCHOP + tafasitamab (12 mg/kg IV, D1, 8, 15) + LEN (25
mg orally, D1–10) (arm B). GCSF and VTE prophylaxis was
mandatory. The primary objective was safety; secondary objectives
included overall response rate (ORR) and PETCR rate at end of
Tx, progressionfree survival, longterm safety, pharmacokinetics
and immunogenicity.
Results: From Dec 2019 to Aug 2020, 83 pts were screened in nine
countries across Europe and the US; 66 were randomized (arm A,
n = 33; arm B, n = 33). Data cutoff: Dec 9, 2020 (study ongoing).
Median age was 64.5 years (range 20–86). Overall, 30% of pts (20/66)
were 70 years old and many had highrisk disease: IPI 2: 28.8%, IPI 3:
45.5%, IPI 4: 25.8%; ECOG PS 0: 47.0%, PS 1: 43.9%, PS 2: 9.1%. Most
pts had stage III/IV disease (92%); 45.5% had bulky disease.
All pts experienced a treatmentemergent adverse event (TEAE).
Grade 3 neutropenia and thrombocytopenia occurred in 54.5% and
12.1% (arm A), and 66.7% and 30.3% (arm B) of pts, respectively. Six pts
in each arm experienced febrile neutropenia. Grade 3 nervous system
disorders occurred in 6.1% of pts in arm A and 12.1% in arm B (most
events were polyneuropathies related to vincristine). Infusionrelated
reactions to both rituximab and tafasitamab occurred in 12.1% (arm A)
and 18.2% (arm B) of pts, and 21.2% (arm A) and 27.3% (arm B) had a
Grade 3 infection and/or infestation (TEAEs by system organ class
FIGURE 1 TEAEs by system organ class and toxicity grade
324
-
SUPPLEMENT ABSTRACTS
shown in Figure 1). Serious TEAEs occurred in 42.4% (arm A) and 51.5%
(arm B) of pts. There were three deaths unrelated to tafasitamab and/
or LEN (sepsis, urosepsis, and COVID19 pneumonia). Dose intensity of
RCHOP was maintained in both arms.
Among 60 pts who completed tumor assessments after cycle 3,
ORR was 89.7% (arm A) and 93.5% (arm B).
Conclusion: These data suggest that RCHOP + tafasitamab or
tafasitamab + LEN is tolerable in pts with Txnaïve DLBCL. Dosing of
RCHOP is unaffected by the addition of tafasitamab. Toxicities were
similar to those expected with RCHOP alone or with LEN. Updated
safety and early efficacy data will be presented at the conference.
EA previously submitted to ASCO and EHA 2021.
The research was funded by: MorphoSys AG, Planegg, Germany
Keywords: Aggressive Bcell nonHodgkin lymphoma
Conflicts of interests pertinent to the abstract
D. Belada
Consultant or advisory role: Roche, Gilead Sciences, JanssenCilag,
Takeda, MorphoSys AG, Debiopharm Group
Research funding: Roche, Gilead Sciences, JanssenCilag, Takeda,
MorphoSys AG, Pharmacyclics, Archigen Biotech, Dr Reddy's
Laboratories
Educational grants: Gilead Sciences, Takeda, Roche
E. Pérez Persona
Consultant or advisory role: Celgene/BMS, Amgen, Janssen, GSK
Educational grants: Roche, Celgene/BMS, Amgen, Janssen, Abbvie,
Jazz Pharmaceutical
Other remuneration: Roche, Celgene/BMS, Amgen, Janssen, Abbvie.
Takeda, Sanofi
P. Klöpfer
Employment or leadership position: MorphoSys AG
B. Brackertz
Employment or leadership position: MorphoSys AG
E. Lohrmann
Employment or leadership position: MorphoSys AG
A. Lahiry
Employment or leadership position: MorphoSys AG
N. Shah
Employment or leadership position: MorphoSys AG
W. Brugger
Employment or leadership position: MorphoSys AG
J. M. Burke
Consultant or advisory role: Genentech/Roche, AbbVie, Seattle Ge-
netics, Bayer, AstraZeneca, Adaptive Biotechnologies, Verastem,
MorphoSys AG, Kura, Epizyme, BeiGene, Kymera
Other remuneration: Seattle Genetics, Beigene
G. S. Nowakowski
Consultant or advisory role: Celgene, MorphoSys AG, Genentech,
Selvita, Debiopharm Group, Kite/Gilead Sciences
Research funding: Celgene, NanoString Technologies, MorphoSys AG
238 | CLINICAL ACTIVITY OF LONCASTUXIMAB TESIRINE
PLUS IBRUTINIB IN NONHODGKIN LYMPHOMA: UPDATED
LOTIS 3 PHASE 1 RESULTS
J. Depaus
1
, N. WagnerJohnston
2
, P. L. Zinzani
3
, T. J. Phillips
4
, J.
Maly
5
, S. Ferrari
6
, E. Bachy
7
, L. J. Bryan
8
, V. Delwail
9
, M. Janakiram
10
,
S. de Guibert
11
, M. Tani
12
, V. Dai
13
, K. Havenith
14
, J. Boni
13
, X. He
13
,
A. ErvinHaynes
13
, C. CarloStella
15
1
CHU UCL Namur site Godinne, Department of Hematology, Yvoir, Belgium,
2
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins
University School of Medicine, Division of Oncology, Baltimore, Maryland,
USA,
3
Università di Bologna, IRCCS Azienda OspedalieroUniversitaria di
Bologna Istituto di Ematologia "Seràgnoli", and Dipartimento di Medicina
Specialistica, Diagnostica e Sperimentale, Bologna, Italy,
4
University of
Michigan, Comprehensive Cancer Center, Ann Arbor, USA,
5
Norton Cancer
Institute, Medical Oncology, Louisville, Kentucky, USA,
6
Azienda Ospeda-
liera Papa Giovanni XXIII, Hematology and Bone Marrow Transplant Unit,
Bergamo, Italy,
7
Hôpital Lyon Sud, Department of Hematology, Pierre
Bénite, France,
8
Georgia Cancer Center at Augusta University, Department
of Medicine, Division of Hematology/Oncology, Augusta, Georgia, USA,
9
Centre Hospitalier Universitaire de Poitiers, Department of Hematology
and Cell Therapy, Poitiers, France,
10
University of Minnesota, Division of
Hematology, Oncology and Transplantation, Minneapolis, Minnesota, USA,
11
Centre Hospitalier Universitaire de Rennes Hôpital Pontchaillou,
Department of Clinical Hematology, Rennes, France,
12
Santa Maria delle
Crioci Hospital, Unit of Hematology, Ravenna, Italy,
13
ADC Therapeutics
America, Inc, Clinical Development, Murray Hill, New Jersey, USA,
14
ADC
Therapeutics (UK) Ltd, Research and Development, London, UK,
15
Humanitas Clinical and Research Center IRCCS, and Humanitas Uni-
versity, Department of Oncology and Hematology, Rozzano, Milan, Italy
Introduction: The treatment of relapsed/refractory (R/R) diffuse
large Bcell lymphoma (DLBCL) and mantle cell lymphoma (MCL)
remains an area of unmet need. Combination therapy using agents
with different mechanisms of action may improve upon therapeutic
outcomes. We investigated the combination of loncastuximab tesir-
ine (Lonca; an antibodydrug conjugate composed of a humanized
antiCD19 monoclonal antibody conjugated to a pyrrolobenzodiaze-
pine dimer toxin) with ibrutinib (a smallmolecule inhibitor of Bru-
ton's tyrosine kinase). Here we present updated safety and efficacy
data from the Phase 1 portion of a Phase 1/2 study (NCT03684694).
Methods: The protocol is a dose escalation and dose expansion, open
label, singlearm, combination study in patients (18 years) with R/R
DLBCL or R/R MCL. The primary objectives of Phase 1 are to char-
acterize the safety and tolerability of Lonca plus ibrutinib, and identify
the recommended Phase 2 dose and schedule. Secondary objectives
include evaluation of antitumor effects. The maximum tolerated dose
SUPPLEMENT ABSTRACTS
-
325
(MTD) was determined during the dose escalation part as Lonca 60 µg/
kg IV every 3 weeks (Q3W) for 2 cycles and oral ibrutinib 560 mg/day
po for up to 1 year. After disease assessment at Week 14, patients with
partial response or stable disease may receive 2 additional cycles of
Lonca every 4 weeks at Cycles 5 and 6.
Results: At data cutoff (January 4, 2021), 30 patients with DLBCL (24
with nongerminal center Bcell [nonGCB] DLBCL and 6 with GCB
DLBCL) and 7 patients with MCL had received the MTD. Median pa-
tient age was 72 years (range 40–91) and 28 (75.7%) had Stage 4
disease. Patients received a median of 2 (range 1–6) prior therapies.
Eight (21.6%) patients were primary refractory and 18 (48.6%) were
refractory to their lastline of therapy; 24 (64.9%) and 17 (45.9%) had
relapsed with firstline and lastline therapy, respectively.
Patients received a median of 2 Lonca cycles (range 1–4) and 4
(range 1–14) ibrutinib cycles. Median treatment duration was 105
days (range 18–379).
Treatmentemergent adverse events (TEAEs) were reported in
37/37 (100%) patients; most common (20%) were thrombocytopenia
(11 [29.7%]), anemia (9 [24.3%]), fatigue, diarrhea, and rash (all 8
[21.6%]). Grade 3 TEAEs were reported in 24/37 (64.9%) patients;
most common (5%) were anemia (4 [10.8%]), neutropenia (4 [10.8%]),
thrombocytopenia (2 [5.4%]), and fatigue (2 [5.4%]). TEAEs leading to
treatment discontinuation occurred in 3 (8.1%) patients.
Overall response rate (ORR; in 36 evaluable patients) was 63.9%
(36.1% and 27.8% for complete and partial response, respectively).
ORR for patients with nonGCB DLBCL, GCB DLBCL, all DLBCL, and
MCL was 66.7%, 20.0%, 58.6%, and 85.7%, respectively (Figure 1).
Conclusions: Results indicate that Lonca 60 µg/kg plus ibrutinib 560
mg has encouraging antitumor activity, with manageable toxicity in
R/R DLBCL or R/R MCL.
The research was funded by: ADC Therapeutics SA
Keywords: CombinationTherapies
Conflicts of interests pertinent to the abstract
J. Depaus
Consultant or advisory role: Takeda, Novartis, Janssen
N. WagnerJohnston
Consultant or advisory role: ADC Therapeutics, Regeneron, CALIBR,
Verastem, Karyopharm, Sanofi, SeaGen, Epizyme, Grunenthal
P. L. Zinzani
Consultant or advisory role: Verastem, MSD, Eusapharma, Sanofi.
ADC Therapeutics (advisory board agreement), Celltrion, Gilead,
JanssenCilag, BMS, Servier, Sandoz, TG Therap., Takeda, Roche,
Kyowa Kirin
T. J. Phillips
Consultant or advisory role: Celgene/BMS, Kite/Gilead, Seattle Ge-
netics, Abbvie/Pharmacyclics, Incyte, Genentech
E. Bachy
Employment or leadership position: Université Claude Bernard Lyon
1, Lyon, France
Consultant or advisory role: Roche, Gilead
Honoraria: Roche, Celgene, Amgen, Janssen, Gilead, Novartis, Sanofi
L. J. Bryan
Employment or leadership position: Augusta University, Augusta, GA
M. Janakiram
Research funding: ADC Therapeutics, FATE Therapeutics, Takeda
Pharmaceuticals
S. de Guibert
Employment or leadership position: CHU Pontchaillou, Rennes,
France
Honoraria: Janssen, Abbvie, Gilead
V. Dai
Employment or leadership position: ADC Therapeutics; SUNY
Research Foundation
Stock ownership: ADC Therapeutics
K. Havenith
Employment or leadership position: ADC Therapeutics
Stock ownership: ADC Therapeutics
J. Boni
Employment or leadership position: ADC Therapeutics
Stock ownership: ADC Therapeutics
X. He
Employment or leadership position: ADC Therapeutics
Stock ownership: ADC Therapeutics
A. ErvinHaynes
Employment or leadership position: ADC Therapeutics
Stock ownership: ADC Therapeutics
C. CarloStella
Consultant or advisory role: Sanofi, ADC Therapeutics, Roche, Kar-
yopharm Therapeutics, Celgene/BristolMyers Squibb, Incyte
Honoraria: BristolMyers Squibb, Janssen Oncology, AstraZeneca
FIGURE 1 ORR by histology
326
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SUPPLEMENT ABSTRACTS
Research funding: ADC Therapeutics, Sanofi, Roche
Educational grants: Roche, Janssen, Takeda, ADC Therapeutics
239 | FINAL ANALYSIS OF A NORDIC LYMPHOMA GROUP
PHASE IB/IIA TRIAL OF PIXANTRONE, ETOPOSIDE,
BENDAMUSTINE AND, IN CD20POSITIVE TUMORS, RITUXIMAB
IN RELAPSED AGGRESSIVE B OR TCELL LYMPHOMAS
F. d'Amore
1
, S. Leppä
2
, T. Relander
3
, T. S. Larsen
4
, P. Brown
5
, J.
Jørgensen
1
, S. Mannisto
2
, P. Lugtenburg
6
, S.K. Leivonen
2
, H. Holte
7
,
U. M. Fagerli
8
, G. F. Lauritzsen
7
, P. Meyer
9
, G. Minotti
10
, P. Menna
10
,
K. Liestøl
11
, H. Toldbod
1
1
Aarhus University Hospital, Hematology, Aarhus N, Denmark,
2
Helsinki
University Hospital, Oncology, Helsinki, Finland,
3
Skane University
Hospital, Oncology, Lund, Sweden,
4
Odense University Hospital,
Hematology, Odense, Denmark,
5
Copenhagen University Hospital,
Hematology, Copenhagen, Denmark,
6
University Medical Center, Erasmus
MC Cancer Institute, Rotterdam, Netherlands,
7
Oslo University Hospital,
Oncology, Oslo, Norway,
8
St Olavs Hospital, Oncology, Trondheim,
Norway,
9
Stavanger University Hospital, Oncology, Stavanger, Norway,
10
University Hospital Campus BioMedico, Clinical Pharmaclogy Labora-
tory, Rome, Italy,
11
University of Oslo, Informatics, Oslo, Norway
Introduction: Multiply relapsed aggressive lymphomas still represent
an unmet clinical need, particularly, if they occur in frail patients (pts).
We developed an outpatient based salvage regimen consisting of
pixantrone, etoposide, bendamustine and, in CD20+ lymphomas,
rituximab (P[R]EBEN). Here we present the final analysis of a phase
1b/2a trial testing this regimen in relapsed aggressive B or Tcell
lymphomas. Treatment refractory pts, i.e. duration of response
(DoR) since last treatment <6 months (mo), were excluded.
Methods and Results: Phase 1b: Five pts were included (median age:
60 yrs; range 3968 yrs). Four had diffuse large cell Bcell (DLBCL) and
1 peripheral Tcell lymphoma (PTCL). All had progressed after autol-
ogous transplant. The pharmacokinetics for pixantrone given in com-
bination (Fig.1a) resembled those of pixantrone monotherapy. Six
serious adverse events (SAEs) were reported among 4 pts: grade 1
(transitory asymptomatic troponin T elevation), grade 2 (nonneu-
tropenic airways infection), grade 3 (nonneutropenic fever, neu-
tropenic fever + anemia, pneumonia), grade 4 (septicemia). Two dose
limiting toxicities (DLTs; neutropenic infection and neutropenia <0.5
10
9
/l of >5 days duration) occurred within cycle 2 at baseline level,
meeting the criteria for maximum tolerated dose (MTD; primary
endpoint, phase1), and defining the phase 2 dose level (P 50 mg/m
2
i.v.
day 1+8, R 375 mg/m
2
i.v. day 1, E 100 mg/m
2
i.v. day 1, Ben 90 mg/m
2
i.
v. day 1).
Phase 2: Sixty pts (M/F ratio:1.3; age range:3984 yrs, median:71
yrs; 37 DLBCL and 23 PTCL) were enrolled and 58 were evaluable.
Median followup was 33 mo (range 853 mo). Grade 34 hematologic
AEs included neutropenia 33%, thrombocytopenia 16%, and anemia
13%. Grade 34 nonhematological AEs included infections 33%, car-
diac 13% and other causes 27%. There were 31 deaths due to: lym-
phoma (22;71%), sepsis (2; 6%) and other causes (7; 23%: 1 lung
carcinoma, 1 acute leukemia, 1 myelodysplasia, 1 lung embolism, 1
allotransplant related and 2 unknown). Of 58 evaluable pts, 38 (66%)
had a complete (CR) and 1 (2%) a partial response, with an overall
response rate (primary endpoint, phase 2) of 68% (B: 51%; T: 70%) .
The median DoR (coprimary endpoint, phase 2) of the 34 pts in CR at
end of treatment was 13 mo (range 0.553+ mo; B: 13 mo; T: 12,5 mo).
Three pts were bridged to allogeneic transplant. The 3yr overall and
progressionfree survival (PFS) rates were 39% and 28%, respectively.
Pts with early metabolic response had a significantly better PFS than
those with active disease (Fig.1b). A correlative analysis on pre
therapeutic biopsies is ongoing to identify gene expression signa-
tures in DLBCL and PTCL related to treatment response.
Conclusion: The P[R]EBEN regimen is a feasible outpatient based
treatment, applicable in frail, heavily pretreated aggressive lym-
phoma pts and shows encouraging CR rates and DoR, particularly in
early responders.
The research was funded by: CTI Life Sciences Limited and Servier
Affaires Médicales
Keywords: Aggressive Bcell nonHodgkin lymphoma, Aggressive T
cell nonHodgkin lymphoma, Combination Therapies
No conflicts of interest pertinent to the abstract.
SUPPLEMENT ABSTRACTS
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327
240 | MOSUNETUZUMAB MONOTHERAPY IN ELDERLY/UNFIT
PTS WITH FIRSTLINE DIFFUSE LARGE BCELL LYMPHOMA
(DLBCL): SAFETY AND EFFICACY REMAIN PROMISING WITH
DURABLE COMPLETE RESPONSES
A. J. Olszewski
1
, A. Avigdor
2
, S. Babu
3
, I. Levi
4
, H. Eradat
5
, U. Abadi
6
,
H. Holmes
7
, M. McKinney
8
, D. Woszczyk
9
, K. Giannopoulos
10
, W.
Jurczak
11
, R. McCord
12
, Y. Xie
13
, K. Sarouei
14
, N. Qayum
15
, C.
O'Hear
16
, G. Sellam
17
, N. Horowitz
18
1
Alpert Medical School, Brown University, Department of Medicine,
Providence, Rhode Island, USA,
2
Sheba Medical Center, Division of
Hematology and BoneMarrow Transplantation, Ramat Gan, Israel,
3
Fort
Wayne Medical Oncology and Hematology, Division of Clinical Research,
Fort Wayne, Indiana, USA,
4
Soroka University Medical Centre, Depart-
ment of Hematology, Be’erSheva, Israel,
5
University of California,
Department of Medicine, Los Angeles, California, USA,
6
Meir Medical
Center, Department of Hematology, Kfar Saba, Israel,
7
Texas Oncology,
Department of Oncology, Dallas, Texas, USA,
8
Duke Cancer Institute,
Division of Hematologic Malignancies and Cellular Therapy, Durham,
North Carolina, USA,
9
University of Opole, Provincial Hospital, Hematol-
ogy Department, Opole, Poland,
10
Medical University of Lublin, Depart-
ment of Experimental Hematooncology, Lublin, Poland,
11
Maria
SklodowskaCurie National Research Institute of Oncology, Department of
Hematology, Kraków, Poland,
12
Genentech, Inc., Oncology Biomarker
Development, South San Francisco, USA,
13
F. HoffmannLa Roche Ltd,
Department of Biometrics, Mississauga, Canada,
14
Genentech, Inc.,
Product Development Safety, South San Francisco, California, USA,
15
Roche Products Ltd, Product Development Oncology, Welwyn Garden
City, UK,
16
Genentech, Inc., Product Development Hematology, South San
Francisco, USA,
17
F. HoffmannLa Roche Ltd, Product Development
Oncology, Basel, Switzerland,
18
Ramban Healthcare Campus, Hematology
Division, Hifa, Israel
Introduction: Elderly/unfit pts with DLBCL, ineligible for standard
firstline (1L) chemoimmunotherapy (CIT) due to frailty and comor-
bidities, often receive no treatment, lowerdose RCHOP, or thera-
pies such as RCVP or Rbendamustine: outcomes are often poor.
Mosunetuzumab (Mosun), a fulllength, humanized, IgG1 CD20xCD3
bispecific antibody, has shown promise in relapsed/refractory DLBCL
(ongoing Ph 1 study NCT02500407). Early data from the Ph 1/2,
multicenter GO40554 study (NCT03677154) show notable efficacy
and tolerability with Mosun monotherapy in elderly/unfit pts with 1L
DLBCL. We report updated GO40554 data.
Methods: Two safetyevaluation cohorts were assessed (Mosun
13.5mg and 30mg) followed by an expansion phase (30mg). Pts aged
80 yr, or 60–79 yr with 1 activity of daily living (ADL) impaired or
instrumental ADL, or reduced cardiac, renal or liver function pre-
cluding fulldose CIT, received optional prednisone (± vincristine)
pretreatment, then IV Mosun on Days (D) 1 (1mg), 8 (2mg) and 15
(13.5 or 30mg) of Cycle (C) 1 and 13.5 or 30mg Mosun on D1 of each
subsequent 21day cycle. Pts with a complete response (CR) stop at 8
cycles; pts with a partial response (PR) or stable disease can continue
to 17 cycles.
Results: By Jan 15 2021, 40 pts received Mosun (13.5mg, n = 8; 30mg ,
n = 7; 30mg expansion, n = 25). Median age was 84 yr (67–100); 27
(67.5%) pts were female, 27 (67.5%) had ECOGPS 0–1, 20 (50%) had
Ann Arbor Stage III–IV and 32 (80%) had an IPI score 2. Pts received a
median of 6 (1–13) cycles; 2 pts in PR continued after C8. 35/40
(87.5%) pts had 1 adverse event (AE), 27 (67.5%) had 1 Mosun
related AE; 15 (37.5%) had a grade (Gr) 3–4 AE (8 Mosunrelated).
Common (>10%) treatmentemergent AEs were cytokine release
syndrome (CRS; n = 9, 22.5%), abdominal pain (n = 7, 17.5%), rash (n =
5, 12.5%) and neutropenia (n = 5, 12.5%); 1 pt had febrile neutropenia.
6 (15%) pts had Gr 1 CRS by ASTCT. 3 (7.5%) pts had Gr 2 CRS, all
managed with supportive care, fluids for hypotension, steroids and
lowflow O
2
, as needed (no tocilizumab, vasopressors, highflow O
2
or
intensive care required). One Gr 1 CRS pt had Mosunrelated Gr 2
neurotoxicity on C1D2 (inability to answer questions, drowsiness and
weakness), resolving after 2 days. 1 pt had a Gr 2 nonserious head-
ache. No pts had fatal or Gr 3 neurologic AEs. From C1–8, 14 (35%)
pts discontinued Mosun due to progressive disease (PD); none dis-
continued due to AEs. Overall response rate in efficacyevaluable pts
(n = 31) was 67.7%; CR rate was 41.9%. Responses post C8 (n [%]) with
Mosun 13.5mg (n = 8) were: 3 (37.5) CR; 3 (37.5) PR; 2 (25) PD; and
post C4 or C8 with Mosun 30mg (n = 23) were: 10 (43.5) CR; 5 (21.7)
PR; 3 (13) PD. Of 13 pts with CR (11 ongoing), 4 durable responses
were seen 12 months from therapy initiation (Figure).
Conclusions: Mosun shows promising efficacy with durable re-
sponses and tolerable safety in elderly/unfit pts with 1L DLBCL and
should be evaluated as a CITfree option.
EA previously submitted to EHA 2021.
The research was funded by: F. HoffmannLa Roche Ltd/Genentech,
Inc. Thirdparty medical writing assistance, under the direction of the
authors, was provided by Katie Buxton and Khalida Rizi of Ashfield
MedComms, an Ashfield Health company, and funded by F.
HoffmannLa Roche Ltd/Genentech, Inc.
Keywords: Aggressive Bcell nonHodgkin lymphoma, Immunotherapy
Conflicts of interests pertinent to the abstract
A. J. Olszewski
Research funding: F. HoffmannLa Roche Ltd/Genentech, Inc., TG
Therapeutics, Adaptive Biotechnologies, Celldex Therapeutics, Pre-
cisionBio, Genmab
A. Avigdor
Consultant or advisory role: Takeda, F. HoffmannLa Roche Ltd,
Gilead, Pfizer
Educational grants: Takeda
Other remuneration: Speakers' bureau: Takeda
S. Babu
Employment or leadership position: Fort Wayne Medical Oncology &
Hematology
328
-
SUPPLEMENT ABSTRACTS
Consultant or advisory role: BristolMyers Squibb, Alexion Pharma-
ceuticals, AstraZeneca, argenx, Boehringer Ingelheim, Bayer, Kite
Pharma, Janssen Oncology, Amgen
Stock ownership: Lutheran hospital, Fort Wayne Medical Oncology &
Hematology
Honoraria: BristolMyers Squibb, Alexion Pharmaceuticals, Lilly,
Bayer, AstraZeneca
Research funding: BristolMyers Squibb, Novartis, Genentech, Inc./F.
HoffmannLa Roche Ltd, AstraZeneca/MedImmune, Janssen
Oncology, Amgen, TG Therapeutics, AbbVie, Lilly, Alexion Pharma-
ceuticals, Merck, Syndax, Nektar, Sanofi, argenx
Educational grants: BristolMyers Squibb, Alexion Pharmaceuticals,
Lilly, Janssen Oncology, Genentech, Inc./F. HoffmannLa Roche Ltd
Other remuneration: Speakers' bureau: Alexion Pharmaceuticals
H. Eradat
Employment or leadership position: UCLA Medical Center, David
Geffen School of Medicine at UCLA
Consultant or advisory role: Genentech, Inc., F. HoffmannLa Roche
Ltd, AbbVie
Honoraria: Genentech, Inc., AbbVie
Research funding: Genentech, Inc., F. HoffmannLa Roche Ltd, Abb-
Vie, AstraZeneca, Atara, Kite, Juno, Acerta, BeiGene, Celgene
Other remuneration: Speakers bureau: Genentech, Inc., AbbVie
U. Abadi
Consultant or advisory role: F. HoffmannLa Roche Ltd
Educational grants: F. HoffmannLa Roche Ltd
H. Holmes
Consultant or advisory role: Kite, Novartis, TG Therapeutics, ADC
Therapeutics, Rigel, Dova, Janssen, BristolMyers Squibb
Other remuneration: Speakers' bureau: Kite, Karyopharm, Dova,
Rigel
M. McKinney
Consultant or advisory role: Kite/Gilead, Seattle Genetics, Molecular
Templates, BTG, Pharmacyclics, Verastem, Genentech, Inc., Celgene
Honoraria: Kite/Gilead
Research funding: UNUM, Molecular Templates, Incyte, BeiGene,
Denovo Biopharma, Pharmacyclics, Nordic Nanovector, Bristol
Myers Squibb, Genentech, Inc., Celgene
Other remuneration: Speakers' bureau: Kite/Gilead
D. Woszczyk
Honoraria: F. HoffmannLa Roche Ltd
Research funding: Millenium, Takeda, JanssenCilag, Novartis, Acerta
Pharma
K. Giannopoulos
Honoraria: F. HoffmannLa Roche Ltd
Educational grants: F. HoffmannLa Roche Ltd
W. Jurczak
Research funding: F. HoffmannLa Roche Ltd
R. McCord
Employment or leadership position: Genentech, Inc.
Stock ownership: F. HoffmannLa Roche Ltd
Y. Xie
Employment or leadership position: F. HoffmannLa Roche Ltd
K. Sarouei
Employment or leadership position: Genentech, Inc.
Stock ownership: F. HoffmannLa Roche Ltd
N. Qayum
Employment or leadership position: F. HoffmannLa Roche Ltd
Stock ownership: F. HoffmannLa Roche Ltd
FIGURE:
Duration of response and time on study by Mosun dosing cohorts
SUPPLEMENT ABSTRACTS
-
329